The incretin effect and its potentiation by glucagon-like peptide 1-based therapies: a revolution in diabetes management

Bibliography

• WILD S, ROGLIC G, GREEN A, SICREE R, KING H: Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes Care (2004) 27(5):1047–1053.
   PubMed Web of Science ®Google Scholar
• MOKDAD AH, FORD ES, BOWMAN BA et al.: Prevalence of obesity, diabetes, and obesity-related health risk factors. IA/VIA (2003) 289(1):76–79.
   Web of Science ®Google Scholar
• Effect of intensive therapy on residual 13-cell function in patients with Type 1 diabetes in the diabetes control and complications trial. A randomized, controlled trial. The Diabetes Control and Complications Trial Research Group. Ann. Intern. Med. (1998) 128(7):517–523.
   Google Scholar
• BALDEWEG SE, YUDKIN JS: Implications of the United Kingdom prospective diabetes study. Prim. Care (1999) 26(4):809–827.
   PubMed Web of Science ®Google Scholar
• ELRICK H, STIMMLER L, HLAD CJ Jr, ARAI Y: Plasma insulin response to oral and intravenous glucose administration. J. Chu. Endocrinol Metab. (1964) 24:1076–1082.
   PubMed Web of Science ®Google Scholar
• McINTYRE N, HOLDSWORTH CD, TURNER DS: Intestinal factors in the control of insulin secretion. .1 Clin. Endocrinol Metab. (1965) 25:1317–1324.
   PubMed Web of Science ®Google Scholar
• PERLEY MJ, KIPNIS DM Plasma insulin responses to oral and intravenous glucose: studies in normal and diabetic subjects. Chu. Invest. (1967) 46(12):1954–62
   PubMed Web of Science ®Google Scholar
• BAYLISS WM, STARLING EH: Mechanism of pancreatic secretion. Physiol (Lond.) (1902) 28:235–334.
   Google Scholar
• MOORE B, EDIE ES, ABRAM JH: On the treatment of diabetes mellitus by acid extract of duodenal mucous membrane. Biochern. J. (1906) 1:28–38.
   PubMedGoogle Scholar
• LA BARRE J, STILL EU. Studies on the physiology of secretin. Am. Physiol (1930) 91:649–653
   Google Scholar
• LOEWER, GREY JS, IVY AC: Is a duodenal hormone involved in carbohydrate metabolism? Am. J. Physiol (1940) 129:659–663.
   Google Scholar
• McINTYREN, HOLSWORTH DC, TURNER DS: New interpretation of oral glucose tolerance. Lancet (1964) 2:20–21.
   Web of Science ®Google Scholar
• DUPREJ, BECK JC: Stimulation of release of insulin by an extract of intestinal mucosa. Diabetes (1966) 15:555–559
   PubMed Web of Science ®Google Scholar
• NAUCK MA, HOMBERGER E, SIEGEL EG et al: Incretin effects of increasing glucose loads in man calculated from venous insulin and C-peptide responses. ./. Chu. Endocrinol Metab. (1986) 63:492–498
   PubMed Web of Science ®Google Scholar
• BROWN JC, PEDERSON RA: A multiparameter study of the action of preparations containing cholecystokinin-pancreozymin. Scand. Castroentero] 1970;5:537–541
   PubMed Web of Science ®Google Scholar
• BROWN JC: A gastric inhibitory polypeptide. I. The amino acid composition and the tryptic peptides. Can. I Biochem. (1971) 49:255–261.
   Google Scholar
• DUPRE J, ROSS SA, WATSON D, BROWN JC: Stimulation of insulin secretion by gastric inhibitory polypeptide in man. J. Chu. Endocrinol Metab. (1973) 37:826–828.
   PubMed Web of Science ®Google Scholar
• BROWN JC, PEDERSON RA: GI hormones and insulin secretion. James VHT (Ed) 5th International Congress on Endocrinology, Excerpta Medica, Hamburg (1976) 2:568–570.
   Google Scholar
• ROSS SA, DUPRE J: Effects of ingestion oftriglyceride or galactose on secretion of gastric inhibitory polypeptide and on response to intravenous glucose in normal and diabetic subjects. Diabetes (1978) 27:327–333.
   PubMed Web of Science ®Google Scholar
• ELAHI D, ANDERSEN DK, BROWN JC et al: Pancreatic a- and 13-cell responses to GIP infusion in normal man. Am. J. Physic'. (1979) 237(2):E185–E191.
   Web of Science ®Google Scholar
• EBERT R, ILLMER K, CREUTZFELDT W: Abolishment of the incretin effect in rats by infusion of gastric inhibitory polypeptide (GIP) antibodies. Scand. Castroenterol (1978) 49:1353.
   Google Scholar
• LUND PK, GOODMAN RH, HABENER JF: Intestinal glucagon mRNA identified by hybridization to a cloned islet cDNA encoding a precursor. Biochem. Biophys. Res. Commun. (1981) 100:1659–1666.
   PubMed Web of Science ®Google Scholar
• LUND PK, GOODMAN RH, MONTMINY MR, DEE PC, HABENER JF: Angler fish islet pre-proglucagon II. Nucleotide and corresponding amino acid sequence of the cDNA. I Biol. Chem. (1983) 258:3280–3284.
   Google Scholar
• BELL GI, SANCHEZ-PESCADOR R, LAYBOURN PJ, NAJARIAN RC: Exon duplication and divergence in the human preproglucagon gene. Nature (1983) 304:368–371.
   PubMed Web of Science ®Google Scholar
• HOLST JJ, ORSKOV C, VAN NIELSEN 0, SCHWARTZ TW: Truncated glucagon-like peptide I, an35.insulin-releasing hormone from the distal gut. FEBS Lett. (1987) 211:169–173.
   Google Scholar
• MOJSOV S, WEIR GC, HABENER JF: Insulinotropin: glucagon-like peptide-I(7-37) co-encoded in the glucagon36.gene is a potent stimulator of insulin release in the perfused rat pancreas. J. Clin. Invest. (1987) 79:616–619.
   Google Scholar
• KREYMANN B, GHATEI MA, WILLIAMS G, BLOOM SR: Glucagon- like peptide-1 (7-36): a physiological37.incretin in marl. Lancet (1987)2:1300–1304.
   PubMed Web of Science ®Google Scholar
• DRUCKER DJ, MOJSOV S, HABENER JF: Cell-specific post-translational processing of preproglucagon expressed from a metallothionein-glucagon fusion gene. J. Biol. Chem. (1986) 261(20:9637–9643.
   PubMedGoogle Scholar
• ORSKOV C, BERSANI M, JOHNSEN AH, HOJRUP P, HOLST JJ: Complete sequences of glucagon-like peptide-1 from human and pig small intestine. J. Biol. Chem. (1989) 264(22):12826–12829.
   PubMed Web of Science ®Google Scholar
• ORSKOV C, RABENHOJ L, WETTERGREN A, KOFOD H, HOLST JF: Tissue and plasma concentrations of amidated and glycine- extended glucagon-like peptide Tin humans. Diabetes (1994) 43.535–539.
   PubMed Web of Science ®Google Scholar
• HOLST JJ, ORSKOV C: Incretin hormones-an update. Land. Clin. Lab. Invest. (2001) 234:75–85.
   Google Scholar
• TINA VILSBOLL T, KRARUP T, MADSBAD S, HOLST JJ: Both GLP-1 and GIP are insulinotropic at basal and postprandial glucose levels and contribute nearly equally to the incretin effect of a meal in healthy subjects. Regul Pep] (2003) 114(2-3):115–121.
   PubMed Web of Science ®Google Scholar
• LEWIS JT, DAYANANDAN B, HABENER JF, KIEFFER TJ: Glucose-dependent insulinotropic polypeptide confers early phase insulin release to oral glucose in rats: demonstration by a receptor antagonist. Endocrinology (2000) 141:3710-3716. TSENG CC, KIEFFER TJ, JARBOE LA, USDIN TB, WOLFE MM: Postprandial stimulation of insulin release by glucose-dependent insulinotropic polypeptide (GIP). Effect of a specific glucose-dependent insulinotropic polypeptide receptor antagonist in the rat. J. Clin. Invest. (1996) 98(10:2440-2445. KOLLIGS F, FEHMANN HC, GOKE R, GOKE B: Reduction of the incretin effect in rats by the glucagon-like peptide 1 receptor antagonist exendin (9–39) amide. Diabetes (1995) 44(1):16–19. EDWARDS CM, TODD JF, MAHMOUDI M et al: Glucagon-like peptide 1 has a physiological role in the control of postprandial glucose in humans: studies with the antagonist exendin 9–39. Diabetes (1999) 48(1):86–93. MIYAWAKI K, YAMADA Y, YANO H et al: Glucose intolerance caused by a defect in the entero-insular axis: a study in gastric inhibitory polypeptide receptor knockout mice. Proc. Nat. Acad. St". USA (1999) 96(26):14843–14847.
   Google Scholar
• SCROCCHI LA, BROWN TJ, MacLUSKY N et al: Glucose intolerance but normal satiety in mice with a null mutation in the glucagon-like peptide 1 receptor gene. Nat. Med. (1996) 2(10:1254–1258.
   PubMedGoogle Scholar
• PERSSON K, GINGERICH RL, NAYAK S, WADA K, WADA E, AHREN B: Reduced GLP-1 and insulin responses and glucose intolerance after gastric glucose in GRP receptor-deleted mice. Am. J. Physiol. Endocrinol. Metab. (2000) 279(5):E956–E962.
   PubMed Web of Science ®Google Scholar
• POLAK JM, BLOOM SR, KUZIO M, BROWN JC, PEARSE AG: Cellular localization of gastric inhibitory polypeptide in the duodenum and jejunum. Gut (1973)14 (4) :284–8.
   PubMed Web of Science ®Google Scholar
• MORTENSEN K, CHRISTENSEN LL, HOLST JJ, ORSKOV C: GLP-1 and GIP are colocalized in a subset of endocrine cells in the small intestine. Regul. Pept. (2003) 114(2-3):189–196.
   PubMed Web of Science ®Google Scholar
• PEDERSON RA, SCHUBERT HE, BROWN JC: Gastric inhibitory polypeptide. Its physiologic release and insulinotropic action in the dog. Diabetes (1975) 24(12):1050–1056.
   Google Scholar
• PEDERSON RA, SCHUBERT HE, BROWN JC: The insulinotropic action of gastric inhibitory polypeptide. Can. .1 Physiol Pharmacol. (1975) 53(2):217–223.
   Google Scholar
• MEIER JJ, GALLWITZ B, SIEPMANN N et al: Gastric inhibitory polypeptide (GIP) dose-dependently stimulates glucagon secretion in healthy human subjects at euglycaemia. Diabetologia (2003) 46(6):798–801.
   PubMed Web of Science ®Google Scholar
• TRUMPER A, TRUMPER K, TRUSHEIM H, ARNOLD R, GOKE B, HORSCH D: Glucose-dependent insulinotropic polypeptide is a growth factor for 0-(INS-1) cells by pleiotropic signaling. Mol. Endocrinol (2001)15(9):1559–1570.
   PubMed Web of Science ®Google Scholar
• MEIER JJ, GOETZE 0, ANSTIPP J etal.: Gastric inhibitory polypeptide does not inhibit gastric emptying in humans. Am. J. Physiol. Endocrinol Metab. (2004) 286(4):E621–E625.
   Google Scholar
• ROTHENBERG ME, EILERTSON CD, KLEIN K et al.: Processing of mouse proglucagon by recombinant prohormone convertase 1 and immunopurified prohormone convertase 2 in vitro. J. Biol. Chem. (1995) 270(17):10136–10146.
   PubMed Web of Science ®Google Scholar
• ROUILLE Y, KANTENGWA S, IRMINGER JC, HALBAN PA: Role of the prohormone convertase PC3 in the processing of proglucagon to glucagon-like peptide 1.1 Biol. Chem. (1997) 272(52):32810–32816.
   Google Scholar
• UGLEHOLDT R, ZHU X, DEACON CE ORSKOV C, STEINER DF, HOLST JJ: Impaired intestinal proglucagon processing in mice lacking prohormone convertase 1. Endocrinology (2004) 145(3):1349–1355.
   PubMed Web of Science ®Google Scholar
• DEACON CF, JOHNSEN AH, HOLST JJ: Human colon produces fully processed glucagon-like peptide-1 (7-36) amide. FEBS Lett. (1995)372(2-3):269–272.
   PubMed Web of Science ®Google Scholar
• PRINTZ H, REITER S, SAMADI N et al.: GLP-1 release in man after lower large bowel resection or intrarectal glucose administration. Digestion (1998) 59(6):689–695.
   PubMed Web of Science ®Google Scholar
• EISSELE R, GOKE R, WILLEMER S et al: Glucagon-like peptide-1 cells in the gastrointestinal tract and pancreas of rat, pig and man. Eur. Clin. Invest. (1992) 22 (4) :283–291.
   PubMed Web of Science ®Google Scholar
• SUGIYAMA K, MANAKA H, KATO T, YAMATANI K, TOMINAGA M, SASAKI H: Stimulation of truncated glucagon-like peptide-1 release from the isolated perfused canine ileum by glucose absorption. Digestion (1994) 55(1):24–28.
   PubMed Web of Science ®Google Scholar
• AHREN B, LARSSON H, HOLST JJ: Reduced gastric inhibitory polypeptide but normal glucagon-like peptide 1 response to oral glucose in postmenopausal women with impaired glucose tolerance. Eur. Endocrinol (1997) 137(2):127–131.
   PubMed Web of Science ®Google Scholar
• ROBERGE JN, BRUBAKER PL: Secretion of proglucagon-derived peptides in response to intestinal luminal nutrients. Endocrinology (1991) 128(6):3169–3174.
   PubMed Web of Science ®Google Scholar
• BRYNES AE, FROST GS, EDWARDS CM, GHATEI MA, BLOOM SR: Plasma glucagon-like peptide-1 (7-36) amide (GLP-1) response to liquid phase, solid phase, and meals of differing lipid composition. Nutrition (1998) 14(5):433–436.
   PubMed Web of Science ®Google Scholar
• ANINI Y, BRUBAKER PL: Muscarinic receptors control glucagon-like peptide 1 secretion by human endocrine L cells. Endocrinology (2003) 144(7):3244–3250.
   PubMed Web of Science ®Google Scholar
• HERRMANN C, GOKE R, RICHTER G, FEHMANN HC, ARNOLD R, GOKE B: Glucagon-like peptide-1 and glucose-dependent insulin-releasing polypeptide plasma levels in response to nutrients. Digestion (1995) 56(2):117–126.
   PubMed Web of Science ®Google Scholar
• ANINI Y, HANSOTIA T, BRUBAKER PL: Muscarinic receptors control postprandial release of glucagon-like peptide-1: in vivo and in vitro studies in rats. Endocrinology (2002) 143(6)2420–2426.
   Google Scholar
• HANSEN L, LAMPERT S, MINEO H, HOLST JJ: Neural regulation of glucagon-like peptide-1 secretion in pigs. Am. J. Physiol Endocrinol Metab. (2004) 287(5):E939–E947.
   PubMed Web of Science ®Google Scholar
• •Thorough study about the neural regulation of GLP-1 secretion.
   Google Scholar
• HERRMANN-RINKE C, VOGE A, HESS M, GOKE B: Regulation of glucagon-like peptide-1 secretion from rat ileum by neurotransmitters and peptides. Endocrinol (1995) 147(1):25–31.
   Web of Science ®Google Scholar
• DAMHOLT AB, BUCHAN AM, KOFOD H: Glucagon-like-peptide-1 secretion from canine L-cells is increased by glucose-dependent-insulinotropic peptide but unaffected by glucose. Endocrinology (1998) 139(4):2085–2091.
   PubMed Web of Science ®Google Scholar
• DEACON CF, WAMBERG S, BIE P, HUGHES TE, HOLST JJ: Preservation of active incretin hormones by inhibition of dipeptidyl peptidase IV suppresses meal-induced incretin secretion in dogs. Endocrinol (2002) 172(2):355–362.
   Web of Science ®Google Scholar
• ROBERGE JN, GRONAU KA, BRUBAKER PL: Gastrin-releasing peptide is a novel mediator of proximal nutrient-induced proglucagon-derived peptide secretion from the distal gut. Endocrinology (1996) 137(6):2383–2388.
   PubMed Web of Science ®Google Scholar
• AHREN B, HUGHES TE: Inhibition of DPP-4 augments insulin secretion in response to exogenously administered GLP-1, GIP, PACAP and GRP in mice. Endocrinology (2004) 16:
   Google Scholar
• HANSEN L, HOLST JJ: The effects of duodenal peptides on glucagon-like peptide-1 secretion from the ileum. A duodeno-ileal loop? Reg& Pept. (2002) 110(1):39–45.
   PubMed Web of Science ®Google Scholar
• BALKS HJ, HOLST JJ, VON ZUR MUHLEN A, BRABANT G: Rapid oscillations in plasma glucagon-like peptide-1 (GLP-1) in humans: cholinergic control of GLP-1 secretion via muscarinic receptors. J Gila Endocrinol Metal). (1997) 82(3):786–790.
   PubMed Web of Science ®Google Scholar
• REIMANN F, GRIBBLE FM: Glucose-sensing in glucagon-like peptide-1-secreting cells. Diabetes (2002) 51:2757–2763.
   PubMed Web of Science ®Google Scholar
• DACHICOURT N, SERRADAS P, BAILBE D, KERGOAT M, DOARE L, PORTHA B: Glucagon-like peptide-1 (7-36)-amide confers glucose sensitivity to previously glucose-incompetent 0-cells in diabetic rats: in vivo and in vitro studies. I Endocrinol (1997) 155(2):369–376.
   Web of Science ®Google Scholar
• BYRNE MM, GLIEM K, WANK U et al.: Glucagon-like peptide 1 improves the ability of the 0-cell to sense and respond to glucose in subjects with impaired glucose tolerance. Diabetes (1998) 47(8):1259–1265.
   PubMed Web of Science ®Google Scholar
• HELLER RS, KIEFFER TJ, HABENER JF: Insulinotropic glucagon-like peptide I receptor expression in glucagon-producing a-cells of the rat endocrine pancreas. Diabetes (1997) 46(5):785–791.
   PubMed Web of Science ®Google Scholar
• FEHMANN HC, HABENER JF. Functional receptors for the insulinotropic hormone glucagon-like peptide-I (7-37) on a somatostatin secreting cell line. FEBS Lett. (1991) 279(2):335–340.
   PubMed Web of Science ®Google Scholar
• HOLZ GG 4TH, KUHTREIBER WM, HABENER JF: Pancreatic 13-cells are rendered glucose-competent by the insulinotropic hormone glucagon-like peptide-1(7-37). Nature (1993) 361(6410):362–365.
   PubMed Web of Science ®Google Scholar
• KANG G, HOLZ GG: Amplification of exocytosis by Ca2'-induced Ca2' release in INS-1 pancreatic 13 cells. .1 Physiol (2003) 546\(Part 1):175–189.
   Google Scholar
• BUTEAU J, RODUIT R, SUSINI S, PRENTKI M: Glucagon-like peptide-1 promotes DNA synthesis, activates phosphatidylinositol 3-kinase and increases transcription factor pancreatic and duodenal homeobox gene 1 (PDX-1) DNA binding activity in 13 (INS-1)-cells. Diabetologia (1999) 42(7):856–864.
   PubMed Web of Science ®Google Scholar
• FEHMANN HC, HABENER JF: Insulinotropic hormone glucagon-like peptide-I(7-37) stimulation of proinsulin gene expression and proinsulin biosynthesis in insulinoma-13 TC-1 cells. Endocrinology (1992) 130(1):159–166.
   PubMed Web of Science ®Google Scholar
• SEUFERT J, KIEFFER TJ, LEECH C et al.: Leptin suppression of insulin secretion and gene expression in human pancreatic islets: implications for the development of adipogenic diabetes mellitus. J. Clin. Endocrinol Metab. (1999) 84(2):670–676.
   PubMed Web of Science ®Google Scholar
• SUSINI S, ROCHE E, PRENTKI M, SCHLEGEL W: Glucose and glucoincretin peptides synergize to induce c-fos, cjun, junB, zif-268, and nur-77gene expression in pancreatic 13(INS-1) cells. FASEB (1998) 12(12):1173–1182.
   PubMed Web of Science ®Google Scholar
• BRAHAM EJ, LEECH CA, LIN JC, ZULEWSKI H, HABENER JF: Insulinotropic hormone glucagon-like peptide-1 differentiation of human pancreatic islet-derived progenitor cells into insulin-producing cells. Endocrinology (2002) 143(8):3152–3161.
   PubMed Web of Science ®Google Scholar
• BULOTTA A, HUT H, ANASTASI E et al.: Cultured pancreatic ductal cells undergo cell cycle re-distribution and 0-cell-like differentiation in response to glucagon-like peptide-1.j. Mol Endocrinol (2002) 29(3):347–360.
   Google Scholar
• LI Y, HANSOTIA T, YUSTA B, RIS F, HALBAN PA, DRUCKER DJ: Glucagon- like peptide-1 receptor signaling modulates 13 cell apoptosis. J. Biol. Chem. (2003) 278(1):471–478.
   PubMed Web of Science ®Google Scholar
• HUT H, NOURPARVAR A, ZHAO X, PERFETTI R: Glucagon-like peptide-1 inhibits apoptosis of insulin-secreting cells via a cyclic 5'-adenosine monophosphate-dependent protein kinase A- and a phosphatidylinositol 3-kinase-dependent pathway. Endocrinology (2003) 144(4):1444–1455.
   PubMed Web of Science ®Google Scholar
• FARILLA L, BULOTTA A, HIRSHBERG B et al: Glucagon-like peptide 1 inhibits cell apoptosis and improves glucose responsiveness of freshly isolated human islets. Endocrinology (2003) 144(12):5149–5158.
   PubMed Web of Science ®Google Scholar
• ORSKOV C, HOLST JJ, NIELSEN OV: Effect of truncated glucagon-like peptide-1 [proglucagon-(78-107) amide] on endocrine secretion from pig pancreas, antrum, and nonantral stomach. Endocrinology (1988) 123(4):2009–2013.
   PubMed Web of Science ®Google Scholar
• GUTNIAK M, ORSKOV C, HOLST JJ, AHREN B, EFENDIC S: Antidiabetogenic effect of glucagon-like peptide-1 (7-36)amide in normal subjects and patients with diabetes mellitus. N Engl. J. Med. (1992) 326(20):1316–1322.
   PubMed Web of Science ®Google Scholar
• •First study that showed the insulinotropic effects of GLP-1 in Type 2 diabetes.
   Google Scholar
• MATSUYAMA T, KOMATSU R, NAMBA M, WATANABE N, ITOH H, TARUI S: Glucagon-like peptide-1 (7-36 amide): a potent glucagonostatic and insulinotropic hormone. Diabetes Res. Clia Pract. (1988) 5(4):281–284.
   PubMed Web of Science ®Google Scholar
• CREUTZFELDT WO, KLEINE N, WILLMS B, ORSKOV C, HOLST JJ, NAUCK MA: Glucagonostatic actions and reduction of fasting hyperglycemia by exogenous glucagon-like peptide 1(7-36) amide in Type I diabetic patients. Diabetes Care (1996) 19(6):580–586.
   PubMed Web of Science ®Google Scholar
• STARK A, MENTLEIN R: Somatostatin inhibits glucagon-like peptide-1-induced insulin secretion and proliferation of RINm5F insulinoma cells. Regul Pept. (2002) 108(2-3):97–102.
   PubMed Web of Science ®Google Scholar
• NAUCK MA, HEIMESAAT MM, BEHLE K et al.: Effects of glucagon-like peptide 1 on counterregulatory hormone responses, cognitive functions, and insulin secretion during hyperinsulinemic, stepped hypoglycemic clamp experiments in healthy volunteers. J. Clin. Endocrinol Metab. (2002) 87(3):1239–1246.
   PubMed Web of Science ®Google Scholar
• SPIELER RC, TROTMAN IF, ADRIAN TE, BLOOM SR, MISIEWICZ JJ, SILK DB: Further characterisation of the 'ileal brake' reflex in man-effect of ileal infusion of partial digests of fat, protein, and starch on jejunal motility and release of neurotensin, enteroglucagon, and peptide YY. Gut (1988) 29(8):1042–1051.
   PubMed Web of Science ®Google Scholar
• MILLER LJ, MALAGELADA JR, TAYLOR WF, GO VL: Intestinal control of human postprandial gastric function: the role of components of jejunoileal chyme in regulating gastric secretion and gastric emptying. Gastroenterology (1981) 80(4):763–769.
   PubMed Web of Science ®Google Scholar
• WETTERGREN A, SCHJOLDAGER B, MORTENSEN PE, MYHRE J, CHRISTIANSEN J, HOLST JJ: Truncated GLP-1 (proglucagon 78-107-amide) inhibits gastric and pancreatic functions in man. Dig. Dis. Sri. (1993) 38(4):665–673.
   PubMed Web of Science ®Google Scholar
• SCHIRRA J, KUWERT P, WANK U et al: Differential effects of subcutaneous GLP-1 on gastric emptying, antroduodenal motility, and pancreatic function in men. Proc. Assoc. Am. Physicians. (1997) 109(1):84–97.
   PubMedGoogle Scholar
• SCHIRRA J, LEICHT P, HILDEBRAND P et al: Mechanisms of the antidiabetic action of subcutaneous glucagon-like peptide-1(7-36)amide in non-insulin dependent diabetes mellitus. Endocrinol. (1998) 156(1):177–186.
   Web of Science ®Google Scholar
• O'DONOVAN DG, DORAN S, FEINLE-BISSET C et al: Effect of variations in small intestinal glucose delivery on plasma glucose, insulin, and incretin hormones in healthy subjects and type 2 diabetes. J. Clin. Endocrinol Metab. (2004) 89(7):3431–3435.
   PubMed Web of Science ®Google Scholar
• NAUCK MA, NIEDEREICHHOLZ U, ETTLER R etal.: Glucagon-like peptide 1 inhibition of gastric emptying outweighs its insulinotropic effects in healthy humans. Am. J. Physiol (1997) 273(5 Part 1):E981–E988.
   Google Scholar
• WETTERGREN A, WOJDEMANN M, HOLST JJ: Glucagon-like peptide-1 inhibits gastropancreatic function by inhibiting central parasympathetic outflow. Am. J. Physic] (1998) 275(5 Part 1):G984–G992.
   Google Scholar
• DELGADO-AROS S, KIM DY, BURTON D etal.: Effect of GLP-1 on gastric volume, emptying, maximum volume ingested, and postprandial symptoms in humans. Am. I Physic] Gastrointest Liver Physiol (2002) 282(3):G424–G431.
   Google Scholar
• FLINT A, RABEN A, ASTRUP A, HOLST JJ: Glucagon-like peptide 1 promotes satiety and suppresses energy intake in humans. J. Clip. Invest. (1998) 101(3):515–520.
   PubMed Web of Science ®Google Scholar
• •First study showing the effects of GLP-1 on food intake.
   Google Scholar
• NASLUND E, KING N, MANSTEN S et al: Prandial subcutaneous injections of glucagon-like peptide-1 cause weight loss in obese human subjects. BE J. Nutr. (2004) 91(3):439–446.
   PubMed Web of Science ®Google Scholar
• GUTZWILLER JP, DREWE J, GOKE B et al.: Glucagon-like peptide-1 promotes satiety and reduces food intake in patients with diabetes mellitus type 2. Am. J. Physic] (1999) 276(5 Part 2):R1541–R1544.
   Google Scholar
• TANG-CHRISTENSEN M, LARSEN PJ, GOKE R et al: Central administration of GLP-1-(7–36) amide inhibits food and water intake in rats. Am .1 Physiol (1996) 271(4 Part 2):R848–R856.
   Google Scholar
• TURTON MD, O'SHEA D, GUNN I et al: A role for glucagon-like peptide-1 in the central regulation of feeding. Nature (1996) 379(6560):69–72.
   PubMed Web of Science ®Google Scholar
• SHUGHRUE PJ, LANE MV, MERCHENTHALER I: Glucagon-like peptide-1 receptor (GLP1-R) mRNA in the rat hypothalamus. Endocrinology (1996) 137(11):5159–5162.
   PubMed Web of Science ®Google Scholar
• UTTENTHAL LO, TOLEDANO A, BLAZQUEZ E: Autoradiographic localization of receptors for glucagon-like peptide-1 (7-36) amide in rat brain. Neuropeptides (1992) 21(3):143–146.
   PubMed Web of Science ®Google Scholar
• VRANG N, PHIFER CB, CORKERN MM, BERTHOUD HR: Gastric distension induces c-fas in medullary GLP-1/2-containing neurons. Am. I Physic] Regul Integr. Comp. Physiol (2003) 285(2):R470–R478.
   PubMed Web of Science ®Google Scholar
• LARSEN PJ, TANG-CHRISTENSEN M, HOLST JJ, ORSKOV C: Distribution of glucagon-like peptide-1 and other preproglucagon-derived peptides in the rat hypothalamus and brainstem. Neuroscience (1997) 77(1):257–270.
   PubMed Web of Science ®Google Scholar
• ORSKOV C, POULSEN SS, MOLLER M, HOLST JJ: Glucagon-like peptide I receptors in the subfornical organ and the area postrema are accessible to circulating glucagon-like peptide I. Diabetes (1996) 45(6):832–835.
   PubMed Web of Science ®Google Scholar
• VILLANUEVA-PENACARRILLO ML, ALCANTARA Al, CLEMENTE F, DELGADO E, VALVERDE I: Potent glycogenic effect of GLP-1(7-36)amide in rat skeletal muscle. Diabetologia (1994) 37(11):1163–1166.
   PubMed Web of Science ®Google Scholar
• MORALES M, LOPEZ-DELGADO MI, ALCANTARA A et al: Preserved GLP-I effects on glycogen synthase a activity and glucose metabolism in isolated hepatocytes and skeletal muscle from diabetic rats. Diabetes (1997) 46(8):1264–1269.
   PubMed Web of Science ®Google Scholar
• MERIDA E, DELGADO E, MOLINA LM, VILLANUEVA-PENACARRILLO ML, VALVERDE I: Presence of glucagon and glucagon-like peptide-147-36)amide receptors in solubilized membranes of human adipose tissue. J. Chit. Endocrinol. Metab. (1993) 77(6):1654–1657.
   PubMedGoogle Scholar
• FURNSINN C, EBNER K, WALDHAUSL W: Failure of GLP-1(7-36)amide to affect glycogenesis in rat skeletal muscle. Diabetologia (1995) 38(7):864–867.
   PubMed Web of Science ®Google Scholar
• BULLOCK BP, HELLER RS, HABENER JF: Tissue distribution of messenger ribonucleic acid encoding the rat glucagon-like peptide-1 receptor. Endocrinology (1996) 137(7):2968–2978.
   PubMed Web of Science ®Google Scholar
• IONUT V, HUCKING K, LIBERTY I, BERGMAN R: Portal GLP-1 reduces peripheral glycemia independent of insulin. Program and abstracts of the 64th Scientific Session of the American Diabetes Association. Florida, USA (June 2004) (Abstract 1412–P).
   Google Scholar
• LARSSON H, HOLST JJ, AHREN B: Glucagon-like peptide-1 reduces hepatic glucose production indirectly through insulin and glucagon in humans. Acta Physiol. Scand. (1997) 160(4):413–422.
   PubMedGoogle Scholar
• DARDEVET D, MOORE MC, NEAL D, DICOSTANZO CA, SNEAD W, CHERRINGTON AD: Insulin-independent effects of GLP-1 on canine liver glucose metabolism: duration of infusion and involvement of hepatoportal region. Am. I Physiol. Endocrinol Metab. (2004) 287(1):E75–E81.
   PubMed Web of Science ®Google Scholar
• WEI Y, MOJSOV S: Tissue-specific expression of the human receptor for glucagon-like peptide-I: brain, heart and pancreatic forms have the same deduced amino acid sequences. FEBS Lett. (1995) 358(3):219–224.
   PubMed Web of Science ®Google Scholar
• BARRAGAN JM, RODRIGUEZ RE, BLAZQUEZ E: Changes in arterial blood pressure and heart rate induced by glucagon-like peptide 1 (7 36) amide in rats. Am. Physic] (1994) 266(3 Part 1):E459–E466.
   Google Scholar
• GROS R, YOU X, BAGGIO LL et al.: Cardiac function in mice lacking the glucagon-like peptide-1 receptor. Endocrinology (2003) 144(6):2242–2252.
   PubMed Web of Science ®Google Scholar
• KANSE SM, KREYMANN B, GHATEI MA, BLOOM SR: Identification and characterization of glucagon-like peptide-1 7-36 amide-binding sites in the rat brain and lung. FEBS Lett. (1988) 241(1-2):209–212.
   PubMed Web of Science ®Google Scholar
• RICHTER G, GOKE R, GOKE B, SCHMIDT H, ARNOLD R: Characterization of glucagon-like peptide-I(7-36)amide receptors of rat lung membranes by covalent cross-linking. FEBS Lett. (1991) 280(2):247–250.
   PubMed Web of Science ®Google Scholar
• DEACON CF, NAUCK MA, MEIER J, HUCKING K, HOLST JJ: Degradation of endogenous and exogenous gastric inhibitory polypeptide in healthy and in type 2 diabetic subjects as revealed using a new assay for the intact peptide. .1 Chit. Endocrinol. Metab. (2000) 85(10):3575–3581.
   Google Scholar
• VILSBOLL T, AGERSO H, KRARUP T, HOLST JJ: Similar elimination rates of glucagon-like peptide-1 in obese type 2 diabetic patients and healthy subjects. Clin. Endocrinol. Metab. (2003) 88(1):220–224.
   Google Scholar
• KIEFFER TJ, McINTOSH CH, PEDERSON RA: Degradation of glucose-dependent insulinotropic polypeptide and truncated glucagon-like peptide 1 in vitro and in vivo by dipeptidyl peptidase IV. Endocrinology (1995) 136(8):3585–3596.
   PubMed Web of Science ®Google Scholar
• DEACON CE JOHNSEN AH, HOLST JJ: Degradation of glucagon-like peptide-1 by human plasma in vitro yields an N-terminally truncated peptide that is a major endogenous metabolite in vivo. J Gila Endocrinol. Metab. (1995) 80(3):952–957.
   PubMed Web of Science ®Google Scholar
• MENTLEIN R, GALLWITZ B, SCHMIDT WE: Dipeptidyl-peptidase IV hydrolyses gastric inhibitory polypeptide, glucagon-like peptide-1 (7-36)amide, peptide histidine methionine and is responsible for their degradation in human serum. Eur. Biochem. (1993) 214(3):829–835.
   PubMedGoogle Scholar
• HUPE-SODMANN K, GOKE R, GOKE B et al: Endoproteolysis of glucagon-like peptide (GLP)-1 (7-36) amide by ectopeptidases in RINm5F cells. Peptides (1997) 18(5):625–632.
   PubMed Web of Science ®Google Scholar
• GAULT VA, PARKER JC, HARRIOTT P, FLATT PR, OHARTE FP: Evidence that the major degradation product of glucose-dependent insulinotropic polypeptide, GIP(3-42), is a GIP receptor antagonist in vivo. J. Endocrinol. (2002) 175(2):525–533.
   PubMed Web of Science ®Google Scholar
• KNUDSEN LB, PRIDAL L: Glucagon-like peptide-146-36) amide is a major metabolite of glucagon-like peptide-1-(7-36) amide after in vivo administration to dogs, and it acts as an antagonist on the pancreatic receptor. Eur. Pharmaco] (1996) 318(2-3):429–435.
   PubMed Web of Science ®Google Scholar
• ROLIN B, DEACON CF, CARR RD, AHREN B: The major glucagon-like peptide-1 metabolite, GLP 1 (9-36) amide, does not affect glucose or insulin levels in mice. Eur. Pharmacol. (2004) 494(2-3):283–288.
   PubMed Web of Science ®Google Scholar
• VAHL TP, PATY BW, FULLER BD, PRIGEON RL, D'ALESSIO DA: Effects of GLP 1 (7 36)NH2, GLP 1 (7 37), and GLP-1- (9-36)NH2 on intravenous glucose tolerance and glucose-induced insulin secretion in healthy humans. J Chit. Endocrinol. Metab. (2003) 88(4):1772–1779.
   PubMed Web of Science ®Google Scholar
• RUIZ-GRANDE C, PINTADO J, ALARCON C, CASTILLA C, VALVERDE I, LOPEZ-NOVOA JM: Renal catabolism of human glucagon-like peptides 1 and 2. Can. J. Physiol. Pharmaco] (1990) 68(12):1568–1573.
   PubMedGoogle Scholar
• MEIER JJ, NAUCK MA, KRANZ D et al: Secretion, degradation, and elimination of glucagon-like peptide 1 and gastric inhibitory polypeptide in patients with chronic renal insufficiency and healthy control subjects. Diabetes (2004) 53(3):654–662.
   PubMed Web of Science ®Google Scholar
• MARGUET D, BAGGIO L, KOBAYASHI T et a]: Enhanced insulin secretion and improved glucose tolerance in mice lacking CD26. Proc. Nat. Acad. ScL USA (2000) 97(12):6874–6879.
   PubMed Web of Science ®Google Scholar
• CONARELLO SL, LI Z, RONAN J et al: Mice lacking dipeptidyl peptidase IV are protected against obesity and insulin resistance. Proc. Nat. Acad. Sci. USA (2003) 100(11):6825–6830.
   PubMed Web of Science ®Google Scholar
• NAGAKURA T, YASUDA N, YAMAZAKI K et al.: Improved glucose tolerance via enhanced glucose-dependent insulin secretion in dipeptidyl peptidase IV-deficient Fischer rats. Biochem. Biophys. Res. Commun. (2001) 284(2):501–506.
   PubMed Web of Science ®Google Scholar
• ULMER AJ, MATTERN T, FELLER AC, HEYMANN E, FLAD HD: CD26 antigen is a surface dipeptidyl peptidase IV (DPP-IV) as characterized by monoclonal antibodies clone TII-19-4-7 and 4EL1 C7. Scand. Immunol (1990) 31(0429–45.
   PubMed Web of Science ®Google Scholar
• FUKASAWA KM, FUKASAWA K, HIRAOKA BY, HARADA M. Comparison of dipeptidyl peptidase IV prepared from pig liver and kidney. Biochim. Biophys. Acta (1981) 657(1):179–189.
   PubMed Web of Science ®Google Scholar
• DEACON CF, PRIDAL L, KLARSKOV L, OLESEN M, HOLST JJ: Glucagon-like peptide 1 undergoes differential tissue-specific metabolism in the anesthetized pig. Am. J. Physiol (1996) 271(3 Part 1):E458–E464.
   Google Scholar
• HANSEN L, DEACON CF, ORSKOV C, HOLST JJ: Glucagon-like peptide-1-(7-36)amide is transformed to glucagon-like peptide-1-(9-36)amide by dipeptidyl peptidase IV in the capillaries supplying the L cells of the porcine intestine. Endocrinology (1999) 140(11):5356–5363.
   PubMed Web of Science ®Google Scholar
• •Excellent study of GLP-1 degradation by local DPP-IV.
   Google Scholar
• DUKE-COHAN JS, MORIMOTO C, ROCKER JA, SCHLOSSMAN SF: A novel form of dipeptidylpeptidase IV found in human serum. Isolation, characterization, and comparison with T lymphocyte membrane dipeptidylpeptidase IV (CD26). ". Biol. Chem. (1995) 270(23):14107–14114.
   Google Scholar
• PAULY RP, ROSCHE F, WERMANN M, McINTOSH CH, PEDERSON RA, DEMUTH HU: Investigation of glucose-dependent insulinotropic polypeptide-(1-42) and glucagon-like peptide 1 -(7-36) degradation in vitro by dipeptidyl peptidase IV using matrix-assisted laser desorption/ ionization-time of flight mass spectrometry. A novel kinetic approach. J. Biol. Chem. (1996) 271(38):23222–23229.
   PubMed Web of Science ®Google Scholar
• LUDWIGA, SCHIEMANN F, MENTLEIN R, LINDNER B, BRANDT E: Dipeptidyl peptidase IV (CD26) on T cells cleaves the CXC chemokine CXCL11 (I-TAC) and abolishes the stimulating but not the desensitizing potential of the chemokine. Leukoc. Biol. (2002) 72(1):183–191.
   PubMed Web of Science ®Google Scholar
• MENTLEIN R, DAHMS P, GRANDT D, KRUGER R: Proteolytic processing of neuropeptide Y and peptide YY by dipeptidyl peptidase IV. Regul Pept. (1993) 49(2):133–144.
   PubMed Web of Science ®Google Scholar
• ZHU L, TAMVAKOPOULOS C, XIE D et al.: The role of dipeptidyl peptidase IV in the cleavage of glucagon family peptides: in vivo metabolism of pituitary adenylate cyclase activating polypeptide- (1-38). J. Biol. Chem. (2003) 278(25):22418–22423.
   PubMed Web of Science ®Google Scholar
• BEDNARCZYK JL, CARROLL SM, MARIN C, McINTYRE BW: Triggering of the proteinase dipeptidyl peptidase IV (CD26) amplifies human T lymphocyte proliferation.Biochem. (1991)46(3):206–218.
   Web of Science ®Google Scholar
• GORRELL MD, WICKSON J, McCAUGHAN GW: Expression of the rat CD26 antigen (dipeptidyl peptidase IV) on subpopulations of rat lymphocytes. Cell. Immunol (1991) 134(1):205–215.
   PubMed Web of Science ®Google Scholar
• SCHARPE S, DE MEESTER I: Purified and cell-bound CD26: enzymatic inhibition, antibody binding profile, and expression on T cells in relation to other surface markers. Verh. K. Acad. Ceneeskd Belg. (1994) 56(6):537–559.
   PubMedGoogle Scholar
• MORIMOTO C, SCHLOSSMAN SF: The structure and function of CD26 in the T-cell immune response. Immunol Rev (1998) 161:55–70.
   PubMed Web of Science ®Google Scholar
• NAUCK M, STOCKMANN F, EBERT R, CREUTZFELDT W: Reduced incretin effect in type 2 (non-insulin-dependent) diabetes. Diabetologia (1986) 29:46–52.
   PubMed Web of Science ®Google Scholar
• •Quantified incretin contribution to C-peptide response in Type 2 diabetes.
   Google Scholar
• VILSBOLL T, KRARUP T, DEACON CF, MADSBAD S, HOLST JJ: Reduced postprandial concentrations of intact biologically active glucagon-like peptide 1 in type 2 diabetic patients. Diabetes (2001) 50(3):609–613.
   PubMed Web of Science ®Google Scholar
• •Shows that in Type 2 diabetes, GIP secretion in response to a meal is preserved whereas GLP-1 secretion is not.
   Google Scholar
• ALAM MJ, KERR JI, CORMICAN K, BUCHANAN KD: Gastric inhibitory polypeptide (GIP) response in diabetes using a highly specific antiserum. Diabet. Med. (1992) 9(6):542–545.
   PubMed Web of Science ®Google Scholar
• ALMIND K, AMBYE L, URHAMMER SA et al.: Discovery of amino acid variants in the human glucose-dependent insulinotropic polypeptide (GIP) receptor: the impact on the pancreatic 13 cell responses and functional expression studies in Chinese hamster fibroblast cells. Diabetologia (1998) 41(101194–1198.
   Google Scholar
• KUBOTA A, YAMADA Y, HAYAMI T et al: Identification of two missense mutations in the GIP receptor gene: a functional study and association analysis with NIDDM: no evidence of association with Japanese NIDDM subjects. Diabetes (1996) 45(12):1701–1705.
   PubMed Web of Science ®Google Scholar
• MEIER JJ, GALLWITZ B, KASK B et al: Stimulation of insulin secretion by intravenous bolus injection and continuous infusion of gastric inhibitory polypeptide in patients with Type 2 diabetes and healthy control subjects. Diabetes (2004) 53\(Suppl. 3):S220–S224.
   Google Scholar
• NAUCK MA, HEIMESAAT MM, ORSKOV C, HOLST JJ, EBERT R, CREUTZFELDT W: Preserved incretin activity of glucagon-like peptide 1 [7-36 amide] but not of synthetic human gastric inhibitory polypeptide in patients with type-2 diabetes mellitus. J. Clin. Invest. (1993) 91(1):301–307.
   PubMed Web of Science ®Google Scholar
• ELAHI D, McALOON-DYKE M, FUKAGAWA NK et al.: The insulinotropic actions of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (7-37) in normal and diabetic subjects. Reg& Pept. (1994) 51(1):63–74.
   PubMed Web of Science ®Google Scholar
• VILSBOLL T, KNOP FK, KRARUP T et al.: The pathophysiology of diabetes involves a defective amplification of the late-phase insulin response to glucose by glucose-dependent insulinotropic polypeptide-regardless of etiology and phenotype. J. Clin. Endocrinol Metab. (2003) 88(10):4897–4903.
   PubMed Web of Science ®Google Scholar
• LUGARI R, DEI CAS A, UGOLOTTI D et al: Evidence for early impairment of glucagon-like peptide 1-induced insulin secretion in human type 2 (non insulin-dependent) diabetes. Horm. Metab. Res. (2002) 34(3):150–154.
   PubMed Web of Science ®Google Scholar
• TOFT-NIELSEN MB, DAMHOLT MB, MADSBAD S et al: Determinants of the impaired secretion of glucagon-like peptide-1 in type 2 diabetic patients. Clin. Endocrinol Metab. (2001) 86(8):3717–3723.
   Google Scholar
• NYHOLM B, WALKER M, GRAVHOLT CH et al: Twenty-four-hour insulin secretion rates, circulating concentrations of fuel substrates and gut incretin hormones in healthy offspring of Type II (non-insulin-dependent) diabetic parents: evidence of several aberrations. Diabetologia (1999) 42(11):1314–1323.
   PubMed Web of Science ®Google Scholar
• VAAG AA, HOLST JJ, VOLUND A, BECK-NIELSEN HB: Gut incretin hormones in identical twins discordant for non-insulin-dependent diabetes mellitus (NIDDM)-evidence for decreased glucagon-like peptide 1 secretion during oral glucose ingestion in NIDDM twins. Eur. Endocrinol (1996) 135(4):425–432.
   PubMed Web of Science ®Google Scholar
• MEIER JJ, HUCKING K, HOLST JJ, DEACON CF, SCHMIEGEL WH, NAUCK MA: Reduced insulinotropic effect of gastric inhibitory polypeptide in first-degree relatives of patients with type 2 diabetes. Diabetes (2001) 50(11):2497–2504.
   PubMed Web of Science ®Google Scholar
• NAUCK MA, EL-OUAGHLIDI A, GABRYS B et al.: Secretion of incretin hormones (GIP and GLP-1) and incretin effect after oral glucose in first-degree relatives of patients with Type 2 diabetes. Reg& Pept. (2004) 122(3):209–217.
   PubMed Web of Science ®Google Scholar
• LEGAKIS IN, TZIORAS C, PHENEKOS C: Decreased glucagon-like peptide 1 fasting levels in type 2 diabetes. Diabetes Care (2003) 26(1):252.
   PubMed Web of Science ®Google Scholar
• SHEN HQ, ROTH MD, PETERSON RG: The effect of glucose and glucagon-like peptide-1 stimulation on insulin release in the perfused pancreas in a non-insulin-dependent diabetes mellitus animal model. Metabolism (1998) 47(9):1042–1047.
   PubMed Web of Science ®Google Scholar
• JIA X, ELLIOTT R, KWOK YN, PEDERSON RA, McINTOSH CH: Altered glucose dependence of glucagon-like peptide I(7-36)-induced insulin secretion from the Zucker (fa/fa) rat pancreas. Diabetes (1995) 44(5):495–500.
   PubMed Web of Science ®Google Scholar
• KJEMS LL, HOLST JJ, VOLUND A, MADSBAD S: The influence of GLP-1 on glucose-stimulated insulin secretion: effects on 13-cell sensitivity in type 2 and nondiabetic subjects. Diabetes (2003) 52(2):380–386.
   PubMed Web of Science ®Google Scholar
• MEIER JJ, GALLWITZ B, SALMEN S, GOETZE 0, HOLST JJ, SCHMIDT WE, NAUCK MA: Normalization of glucose concentrations and deceleration of gastric emptying after solid meals during intravenous glucagon-like peptide 1 in patients with Type 2 diabetes. J Clin. Endocrinol Metab. (2003) 88(6):2719–2725.
   PubMed Web of Science ®Google Scholar
• RACHMAN J, BARROW BA, LEVY JC, TURNER RC: Near-normalisation of diurnal glucose concentrations by continuous administration of glucagon-like peptide-1 (GLP-1) in subjects with NIDDM. Diabetologia (1997) 40(2):205–211.
   PubMed Web of Science ®Google Scholar
• DEACON CF, NAUCK MA, TOFT-NIELSEN M, PRIDAL L, WILLMS B, HOLST JJ: Both subcutaneously and intravenously administered glucagon-like peptide I are rapidly degraded from the NH2-terminus in type II diabetic patients and in healthy subjects. Diabetes (1995) 44(9):1126–1131.
   PubMed Web of Science ®Google Scholar
• NAUCK MA, WOLLSCHLAGER D, WERNER J et al: Effects of subcutaneous glucagon-like peptide 1 (GLP-1[7-36 amide]) in patients with NIDDM. Diabetologia (1996) 39(12):1546–1553.
   PubMed Web of Science ®Google Scholar
• TODD JF, WILDING JP, EDWARDS CM, KHAN FA, GHATEI MA, BLOOM SR: Glucagon-like peptide-1 (GLP-1): a trial of treatment in non-insulin-dependent diabetes mellitus. Eur. Clin. Invest. (1997) 27(6):533–536.
   PubMed Web of Science ®Google Scholar
• TOFT-NIELSEN MB, MADSBAD S, HOLST JJ. Continuous subcutaneous infusion of glucagon-like peptide 1 lowers plasma glucose and reduces appetite in Type 2 diabetic patients. Diabetes Care (1999) 22(7):1137–1143.
   Google Scholar
• ZANDER M, MADSBAD S, MADSEN JL, HOLST JJ: Effect of 6-week course of glucagon-like peptide 1 on glycaemic control, insulin sensitivity, and 13-cell function in Type 2 diabetes: a parallel-group study. Lancet (2002) 359(9309):824=h830.
   Web of Science ®Google Scholar
• •Shows the antidiabetogenic effects of continuous GLP-1 infusion over 6 weeks.
   Google Scholar
• JUNTTI-BERGGREN L, PIGON J, KARPE F et al: The antidiabetogenic effect of GLP-1 is maintained during a 7-day treatment period and improves diabetic dyslipoproteinemia in NIDDM patients. Diabetes Care (1996) 19(11):1200–1206.
   PubMed Web of Science ®Google Scholar
• LARSEN J, HYLLEBERG B, NG K, DAMSBO P: Glucagon-like peptide-1 infusion must be maintained for 24 h/day to obtain acceptable glycemia in type 2 diabetic patients who are poorly controlled on sulphonylurea treatment. Diabetes Care (2001) 24(8):1416–1421.
   PubMed Web of Science ®Google Scholar
• MENEILLY GS, GREIG N, TILDESLEY H, HABENER JF, EGAN JM, ELAHI D: Effects of 3 months of continuous subcutaneous administration of glucagon-like peptide 1 in elderly patients with Type 2 diabetes. Diabetes Care (2003) 26(10):2835–2841.
   PubMed Web of Science ®Google Scholar
• ZANDER M, CHRISTIANSEN A, MADSBAD S, HOLST JJ: Additive effects of glucagon-like peptide 1 and pioglitazone in patients with Type 2 diabetes. Diabetes Care (2004) 27(8):1910–1914.
   PubMed Web of Science ®Google Scholar
• DEACON CF, KNUDSEN LB, MADSEN K, WIBERG FC, JACOBSEN 0, HOLST JJ: Dipeptidyl peptidase IV resistant analogues of glucagon-like peptide-1 which have extended metabolic stability and improved biological activity. Diabetologia (1998) 41(3):271–278.
   PubMed Web of Science ®Google Scholar
• ENG J, KLEINMAN WA, SINGH L, SINGH G, RAUFMAN JP: Isolation and characterization of exendin-4, an exendin-3 analogue, from Heloderma suspectum venom. Further evidence for an exendin receptor on dispersed acini from guinea pig pancreas. J. Biol. Chem. (1992) 267(11):7402–7405.
   Google Scholar
• •First report of exenatide isolation from Heloderma suspectum venom.
   Google Scholar
• THORENS B, PORRET A, BUHLER L, DENG SP, MOREL P, WIDMANN C. Cloning and functional expression of the human islet GLP-1 receptor. Demonstration that exendin-4 is an agonist and exendin-(9–39) an antagonist of the receptor. Diabetes (1993) 42(10:1678–1682.
   Google Scholar
• SCHEPP W, SCHMIDTLER J, RIEDEL T et al: Exendin-4 and exendin-(9-39)NH2: agonist and antagonist, respectively, at the rat parietal cell receptor for glucagon-like peptide 1 (7 36)NH2. Eur. Pharmacol (1994) 269(2):183–191.
   PubMed Web of Science ®Google Scholar
• GOKE R, FEHMANN HC, LINN T et al.: Exendin-4 is a high potency agonist and truncated exendin-(9–39)-amide an antagonist at the glucagon-like peptide 1-(7–36)-amide receptor of insulin-secreting 3-cells. .1 Biol. Chem. (1993) 268(26):19650–19655.
   Google Scholar
• EDWARDS CM, STANLEY SA, DAVIS R et al.: Exendin-4 reduces fasting and postprandial glucose and decreases energy intake in healthy volunteers. Am. Physiol Endocrinol Metab. (2001) 281(1):E155–E161.
   PubMed Web of Science ®Google Scholar
• THUM A, HUPE-SODMANN K, GOKE R, VOIGT K, GOKE B, McGREGOR GP: Endoproteolysis by isolated membrane peptidases reveal metabolic stability of glucagon-like apeptide-1 analogs, exendins-3 and -4. Exp Clic'. Endocrinol Diabetes (2002) 110(3):113–118.
   PubMed Web of Science ®Google Scholar
• HUPE-SODMANN K, McGREGOR GP, BRIDENBAUGH R et al: Characterisation of the processing by human neutral endopeptidase 24.11 of GLP-1(7–36) amide and comparison of the substrate specificity of the enzyme for other glucagon-like peptides. Regul Pept. (1995) 58(3):149–156.
   Google Scholar
• PARKES D, JODKA C, SMITH PAM et al.: Pharmacokinetic actions of exendin-4 in the rat: Comparison with glucagon-like peptide-1. Drug Dedve. Res. (2001) 53:260–267.
   Web of Science ®Google Scholar
• GREIG NH, HOLLOWAY HW, DE ORE KA et al: Once daily injection of exendin-4 to diabetic mice achieves long-term beneficial effects on blood glucose concentrations. Diabetologia (1999) 42(1):45–50.
   PubMed Web of Science ®Google Scholar
• PARKES DG, PITTNER R, JODKA C, SMITH P, YOUNG A: Insulinotropic actions of exendin-4 and glucagon-like peptide-1 in vivo and in vitro. Metabolism (2001) 50(5):583–589.
   PubMed Web of Science ®Google Scholar
• XU G, STOFFERS DA, HABENER JF, BONNER-WEIR S: Exendin-4 stimulates both 0-cell replication and neogenesis, resulting in increased 0-cell mass and improved glucose tolerance in diabetic rats. Diabetes (1999) 48(12):2270–2276.
   PubMed Web of Science ®Google Scholar
• HILES R, CARPENTER T, SEROTA D et al.: Exenatide does not cause pancreatic tumors or malignancies in rats and mice following a 2 year period of exposure. 64th Scientific Session of the American Diabetes Association. Florida, USA (2004) (Abstract 1585–P).
   Google Scholar
• SILVESTRE RA, RODRIGUEZ-GALLARDO J, EGIDO EM, MARCO J: Interrelationship among insulin, glucagon and somatostatin secretory responses to exendin-4 in the perfused rat pancreas. Eur. Pharmacol (2003) 469(1-3):195–200.
   PubMed Web of Science ®Google Scholar
• SZAYNA M, DOYLE ME, BETKEY JA et al.: Exendin-4 decelerates food intake, weight gain, and fat deposition in Zucker rats. Endocrinology (2000) 141(6):1936–1941.
   PubMed Web of Science ®Google Scholar
• GEDULIN B, LAWLER R, JODKA C, YOUNG A: Amylin inhibits pentagastrin-stimulated gastric acid secretion: comparison with glucagon-like peptide-1 and exendin-4. Diabetes 46(1997) (Suppl. 1):188A.
   Google Scholar
• BAGGIO LL, KIM JG, DRUCKER DJ: Chronic exposure to GLP-1R agonists promotes homologous GLP-1 receptor desensitization in vitro but does not attenuate GLP-1R-dependent glucose homeostasis in vivo. Diabetes (2004) 53\(Suppl. 3):5205–5214.
   Google Scholar
• KOLTERMAN OG, BUSE JB, FINEMAN MS et al.: Synthetic exendin-4 (exenatide) significantly reduces postprandial and fasting plasma glucose in subjects with type 2 diabetes. J Endocrinol Metab. (2003) 88(7):3082–3089.
   PubMed Web of Science ®Google Scholar
• DEGN KB, BROCK B, JUHL CB et al: Effect of intravenous infusion of exenatide (synthetic exendin-4) on glucose-dependent insulin secretion and counterregulation during hypoglycemia. Diabetes (2004) 53(9):2397–2403.
   PubMed Web of Science ®Google Scholar
• FEHSE FC, TRAUTMANN ME, HOLST JJ et al.: Effects of Exenatide on First and Second Phase Insulin Secretion in Response to Intravenous Glucose in Subjects with Type 2 Diabetes. Program and abstracts of the 64th Scientific Session of the American Diabetes Association. Florida, USA (June 2004) (Abstract 351-0R).
   Google Scholar
• CALARA F, TAYLOR K, HAN J et al.: Effect of Injection Site on Relative Bioavailability of Exenatide (Synthetic Exendin-4). Program and abstracts of the 64th Scientific Session of the American Diabetes Association. Florida, USA (June 2004) (Abstract 508–P).
   Google Scholar
• POON T, TAYLOR K, NIELSEN L et al.: Exenatide (synthetic exendin-4) continuously improves glucose control over three months in patients with type 2 diabetes. Program and abstracts of the 63rd Scientific Session of the American Diabetes Association. Louisiana, USA (June 2003) (Abstract 560–P).
   Google Scholar
• FINEMAN MS, BICSAK TA, SHEN LZ et al: Effect on glycemic control of exenatide (synthetic exendin-4) additive to existing metformin anclior sulfonylurea treatment in patients with Type 2 diabetes. Diabetes Care (2003) 26(8):2370–2377.
   PubMed Web of Science ®Google Scholar
• FINEMAN MS, SHEN LZ, TAYLOR K, KIM DD, BARON AD: Effectiveness of progressive dose-escalation of exenatide (exendin-4) in reducing dose-limiting side effects in subjects with type 2 diabetes. Diabetes Metab. Res Rev (2004) 20(5):411–417.
   PubMed Web of Science ®Google Scholar
• POON T, NELSON P, LOVE K et al: Twenty-eight day dose-response study with Exenatide (Synthetic Exendin-4)in subjects with type 2 diabetes treated with metformin or with diet and exercise. Program and abstracts of the 64th Scientific Session of the American Diabetes Association. Florida, USA (June 2004) (Abstract 598–P).
   Google Scholar
• BUSE JB, HENRY RR, HAN J, KIM DD, FINEMAN MS, BARON AD: Exenatide-113 Clinical Study Group. Effects of exenatide (exendin-4) on glycemic control over 30 weeks in sulfonylurea-treated patients with Type 2 diabetes. Diabetes Care (2004) 27(11):2628–2635.
   Google Scholar
• ••AMIGO II.
   Google Scholar
• DE FRONZO R, RATNER R, HAN J, KIM D, FINEMAN M, BARON A: Effects of exenatide (synthetic exendin-4) on glycemic Control and weight over 30 weeks in metformin-treated patients with type 2 diabetes. Program and abstracts of the 64th Scientific Session of the American Diabetes Association. Florida, USA (June 2004) (Abstract 6-LB). AMIGO I.
   Google Scholar
• KENDALL DM, RIDDLE MC, ZHUANG D, KIM DD, FINEMAN MS, BARON AD: Effects of exenatide (synthetic exendin-4) on glycemicc and weight over 30 weeks in patients with type 2 diabetes treated with metformin and a sulfonylurea. Program and abstracts of the 64th Scientific Session of the American Diabetes Association. Florida, USA (June 2004) (Abstract 10-LB).
   Google Scholar
• ••AMIGO III. These three studies areknown as AMIGO I - III. They show exenatide efficacy in patients taking metformin, SFU or the combination of both, over a 30-week period.
   Google Scholar
• ELBROND B, JAKOBSEN G, LARSEN S et al.: Pharmacokinetics, pharmacodynamics, safety, and tolerability of a single-dose of NN-2211, a long-acting glucagon-like peptide 1 derivative, in healthy male subjects. Diabetes Care (2002) 25(8):1398–1404.
   PubMed Web of Science ®Google Scholar
• AGERSO H, JENSEN LB, ELBROND B, ROLAN P, ZDRAVKOVIC M: The pharmacokinetics, pharmacodynamics, safety and tolerability of NN-2211, a new long-acting GLP-1 derivative, in healthy men. Diabetologia (2002) 45(2):195–202.
   PubMed Web of Science ®Google Scholar
• RIBEL U, LARSEN MO, ROLIN B et al.: NN-2211: a long-acting glucagon-like peptide-1 derivative with anti-diabetic effects in glucose-intolerant pigs. Eur. Pharmacol (2002) 451(2):217–225.
   PubMed Web of Science ®Google Scholar
• STURIS J, GOTFREDSEN CF, ROMER J et al: GLP-1 derivative liraglutide in rats 724 Expert Op/n. Investig. Drugs (2005) 14(6) with 0-cell deficiencies: influence of metabolic state on 0-cell mass dynamics. BE Pharmacol (2003) 140(1):123–132.
   Google Scholar
• ROLIN B, LARSEN MO, GOTFREDSEN CF et al: The long-acting GLP-1 derivative NN-2211 ameliorates glycemia and increases 0-cell mass in diabetic mice. Am. Physiol Endocrinol Metab. (2002) 283(4):E745–E752.
   PubMed Web of Science ®Google Scholar
• LARSEN PJ, FLEDELIUS C, KNUDSEN LB, TANG-CHRISTENSEN M: Systemic administration of the long-acting GLP-1 derivative NN-2211 induces lasting and reversible weight loss in both normal and obese rats. Diabetes (2001) 50(11):2530–2539.
   PubMed Web of Science ®Google Scholar
• JUHL CB, HOLLINGDAL M, STURIS J et al.: Bedtime administration of NN-2211, a long-acting GLP-1 derivative, substantially reduces fasting and postprandial glycemia in type 2 diabetes. Diabetes (2002) 51(2):424–429.
   PubMed Web of Science ®Google Scholar
• CHANG AM, JAKOBSEN G, STURIS J et al: The GLP-1 derivative NN-2211 restores 3-cell sensitivity to glucose in type 2 diabetic patients after a single dose. Diabetes. (2003) 52(7):1786–1791.
   PubMed Web of Science ®Google Scholar
• NAUCK M, EL-OUAGHLIDI A, HOMPESH M, JACOBSON J, ELBROEND J: No impairment of hypoglycemia counterregulation via glucagon with NN2211, a GLP-1 derivative, in subjects with type 2-diabetes. Program and abstracts of the 63rd Scientific Session of the American Diabetes Association. Louisiana, USA (June 2003) (Abstract 550–P).
   Google Scholar
• DEGN KB, JUHL CB, STURIS J et al.: One week's treatment with the long-acting glucagon-like peptide 1 derivative liraglutide (NN-2211) markedly improves 24-h glycemia and a- and 0-cell function and reduces endogenous glucose release in patients with type 2 diabetes. Diabetes (2004) 53(5):1187–1194.
   PubMed Web of Science ®Google Scholar
• MADSBAD S, SCHMITZ 0, RANSTAM J, JAKOBSEN G, MATTHEWS DR: NN-2211-1310 INTERNATIONAL STUDY GROUP Improved glycemic control with no weight increase in patients with type 2 diabetes after once-daily treatment with the long-acting glucagon-like peptide 1 analog liraglutide (NN-2211): a 12-week, double-blind, randomized, controlled trial. Diabetes Care (2004) 27(6):1335–1342.
   PubMed Web of Science ®Google Scholar
• HARDER H, NIELSEN L, TU DT, ASTRUP A: The effect of liraglutide, a long-acting glucagon-like peptide 1 derivative, on glycemic control, body composition, and 24-h energy expenditure in patients with type 2 diabetes. Diabetes Care (2004) 27(8):1915–1921.
   PubMed Web of Science ®Google Scholar
• NAUCK M, HOMPESCH M, FILIPCZAK R et al: Liraglutide significantly improves glycemic control and reduces body weight compared with glimepiride as add-on to metformin in type 2 diabetes. Program and abstracts of the 64th Scientific Session of the American Diabetes Association. Florida, USA (June 2004) (Abstract 356-0R).
   Google Scholar
• GIANNOUKAKIS N: CJC-1131. ConjuChem. Curc Opin. Investig. Drugs (2003) 4(10):1245–1249.
   PubMedGoogle Scholar
• KIM JG, BAGGIO LL, BRIDON DP et al.: Development and characterization of a glucagon-like peptide 1-albumin conjugate: the ability to activate the glucagon-like peptide 1 receptor in vivo. Diabetes (2003) 52(3):751–759.
   PubMed Web of Science ®Google Scholar
• LAWRENCE B, DREYFUS J, WEN S, GUIVARC'H P, DRUCKER D, CASTAIGNE JP: CJC-1131, a Long Acting GLP-1 Derivative, Exhibits an Extended Pharmacokinetic Profile in Healthy Human Volunteers. Program and abstracts of the 63rd. Scientific Session of the American Diabetes Association. Louisiana,USA (June 2003) (Abstract 534–P).
   Google Scholar
• WEN S, CHATENOUD L, LAWRENCE B, FRANCO P, CASTAIGNE JP, BACH JF: Lack of Immunogenicity of CJC-1131, a Long Acting GLP-1 Analog for the Treatment of Type 2 Diabetes. Program and abstracts of the 64th Scientific Session of the American Diabetes Association. Florida, USA (June 2004) (Abstract 634–P).
   Google Scholar
• GUIVARCH PH, CASTAIGNE JP, PESLHERBE GL, DREYFUS JH, DRUCKER DJ: CJC-1131, along acting GLP-1 analog safely normalizes post-prandial glucose excursion and fasting glycemia in type 2 diabetes mellitus. Program and abstracts of the 64th Scientific Session of the American Diabetes Association. Florida, USA (June 2004) (Abstract 535–P).
   Google Scholar
• BAGGIO LL, HUANG Q, BROWN TJ, DRUCKER DJ: A recombinant human glucagon-like peptide (GLP)-1-albumin protein (albugon) mimics peptidergic activation of GLP-1 receptor-dependent pathways coupled with satiety, gastrointestinal motility, and glucose homeostasis. Diabetes (2004) 53(9):2492–2500.
   PubMed Web of Science ®Google Scholar
• THORKILDSEN C, NEVE S, LARSEN BD, MEIER E, PETERSEN JS: Glucagon-like peptide 1 receptor agonist ZP10A increases insulin mRNA expression and prevents diabetic progression in db/db Pharmacol Exp. Ther. (2003) 307(2):490–496.
   Google Scholar
• TRAUTMANN M, CHEN CE CHAPPELL J et al.: THE GFFH STUDY GROUP: LY-307161 SR, a Long-Acting GLP-1 Analog, Improved Glycemic Control in Patients with Type 2 Diabetes. Program and abstracts of the 63rd. Scientific Session of the American Diabetes Association. Louisiana,USA (June 2003) (Abstract 582–P).
   Google Scholar
• HANSOTIA T, BAGGIO LL, DELMEIRE D et al.: Double incretin receptor knockout (DIRKO) mice reveal an essential role for the enteroinsular axis in transducing the glucoregulatory actions of DPP-IV inhibitors. Diabetes (2004) 53(5):1326–1335.
   PubMed Web of Science ®Google Scholar
• MIKA A, ADLER A, FARB T et al: 7 Day (AM or PM) Inhibition of DPPIV (Dipeptidyl Peptidase IV) Show No Additional Benefit on Glucose Lowering or Insulin Sensitization over Acute Dosing. Program and abstracts of the 64th Scientific Session of the American Diabetes Association. Florida, USA (June 2004) (Abstract 2382-P 0) .
   Google Scholar
• POSPISILIK JA, STAFFORD SG, DEMUTH HU, MCINTOSH CH, PEDERSON RA: Long-term treatment with dipeptidyl peptidase IV inhibitor improves hepatic and peripheral insulin sensitivity in the VDF Zucker rat: a euglycemic-hyperinsulinemic clamp study. Diabetes (2002) 51(9):2677–83.
   PubMed Web of Science ®Google Scholar
• REIMER MK, HOLST JJ, AHREN B: Long-term inhibition of dipeptidyl peptidase IV improves glucose tolerance and preserves islet function in mice. Eur. Endocrinol (2002) 146(5):717–727.
   PubMed Web of Science ®Google Scholar
• PETROV A, IPPOLITO D, McCANN P et al: Female ZDF Rat Model of Diabetes: Effect of Therapeutic Administration of DP-IV inhibitor (25,35)-Isoleucyl Thiazolidide. Program and abstracts of the 64th Scientific Session of the American Diabetes Association. Florida, USA (June 2004) (Abstract 1415–P).
   Google Scholar
• GREISEN H, CARR R, SVENDSEN 0, BODVARSDOTTIR T: Dipeptidyl 725 Expert Op/n. lnvestig. Drugs (2005) 14(6) Peptidase IV Inhibition Improves Glucose Tolerance without a Concomitant Rise in Plasma Insulin in the GK Rat. Program and abstracts of the 63rd. Scientific Session of the American Diabetes Association. Louisiana,USA (June 2003) (Abstract 1397–P).
   Google Scholar
• LETTING B, NICHOLS E, BIFTU T et al.: Inhibition of dipeptidyl peptidase IV does not attenuate T cell activation in vitro. Program and abstracts of the 64th Scientific Session of the American Diabetes Association. Florida, USA (June 2004) (Abstract 6-0R).
   Google Scholar
• LANKAS G, LETTING B, SINHA ROY R et al.: Inhibition of DPP8/9 results in toxicity in preclinical species: potential importance of selective dipeptidyl peptidase IV inhibition for the treatment of type 2 DM. Program and abstracts of the 64th Scientific Session of the American Diabetes Association. Florida, USA (June 2004) (Abstract 7-0R).
   Google Scholar
• DEACON CE HUGHES TE, HOLST JJ: Dipeptidyl peptidase IV inhibition potentiates the insulinotropic effect of glucagon-like peptide 1 in the anesthetized pig. Diabetes (1998) 47(5):764–769.
   PubMed Web of Science ®Google Scholar
• POSPISILIK JA, STAFFORD SG, DEMUTH HU etal.: Long-term treatment with the dipeptidyl peptidase IV inhibitor P32/98 causes sustained improvements in glucose tolerance, insulin sensitivity, hyperinsulinemia, and 13-cell glucose responsiveness in VDF (fa/fa) Zucker rats. Diabetes (2002) 51(4):943–950.
   Google Scholar
• BALKAN B, KWASNIK L, MISERENDINO R, HOLST JJ, LI X: Inhibition of dipeptidyl peptidase IV with NVP-DPP728 increases plasma GLP-1 (7-36 amide) concentrations and improves oral glucose tolerance in obese Zucker rats. Diabetologia (1999) 42(11):1324–1331.
   PubMed Web of Science ®Google Scholar
• VILLHAUER EB, BRINKMAN JA, NADERI GB et al.:1- [[(3-hydroxy-1-adamantyl)amino]acety11-2-cyano- (5)-pyrrolidine: a potent, selective, and orally bioavailable dipeptidyl peptidase IV inhibitor with antihyperglycemic properties. Med. Chem. (2003) 46(13):2774–2789.
   Web of Science ®Google Scholar
• AHREN B, SIMONSSON E, LARSSON H et al: Inhibition of dipeptidyl peptidase IV improves metabolic control over a 4-week study period in Type 2 diabetes. Diabetes Care (2002) 25(5):869–875.
   PubMed Web of Science ®Google Scholar
• DARDICK B, SCHWARZTKOPF C, STEVENS D et al: The Dipeptidyl Peptidase IV Inhibitor NVP-LAF237 Improves Metabolic Control in Diabetic and Nondiabetic Cynomolgus Monkeys. Program and abstracts of the 63rd. Scientific Session of the American Diabetes Association. Louisiana,USA (June 2003) (Abstract 1391–P).
   Google Scholar
• DARDICK B, VALENTIN M, SCHWARZTKOPF C etal.: NVP-LAF-237, a dipeptidyl peptidase IV inhibitor, improves glucose tolerance and delays gastric emptying in obese insulin resistant cynomolgus monkeys. Program and abstracts of the 63rd. Scientific Session of the American Diabetes Association. Louisiana,USA (June 2003) (Abstract 1392–P).
   Google Scholar
• WINZELL MS, AHREN B. The high-fat diet-fed mouse: a model for studying mechanisms and treatment of impaired glucose tolerance and Type 2 diabetes. Diabetes (2004) 53\(Suppl. 3):5215–5219.
   Google Scholar
• AHREN B, LANDIN-OLSSON M, JANSSON PA, SVENSSON M, HOLMES D, SCHWEIZER A: Inhibition of dipeptidyl peptidase-4 reduces glycemia, sustains insulin levels, and reduces glucagon levels in Type 2 diabetes. I Clin. Endocrinol Metab. (2004) 89(5):2078–2084.
   PubMed Web of Science ®Google Scholar
• PRATLEY R, GALBREATH E. Twelve-week monotherapy with the DPP-4 inhibitor, LAF-237 improves glycemic control in patients with Type 2 diabetes (T2DM). Program and abstracts of the 64th Scientific Session of the American Diabetes Association. Florida, USA (June 2004) (Abstract 355-0R).
   Google Scholar
• AHREN B, GOMIS R, STANDL E, MILLS D, SCHWEIZER A: Twelve- and 52-week efficacy of the dipeptidyl peptidase IV inhibitor LAF237 in metformin-treated patients with Type 2 diabetes. Diabetes Care (2004) 27(12):2874–2880.
   PubMed Web of Science ®Google Scholar
• •Important study testing long-term efficacy and tolerability of yildagliptin.
   Google Scholar
• ROLIN B, NYGAARD H, WILKEN M, KANSTRUP AB, CARR RD: The Novel, Xanthine-Based, DPPIV Inhibitor NN7201 and LAF237 Improve Glucose Tolerance, but do Not Prevent Progression of Diabetes in Zucker Diabetic Fatty Rats. Program and abstracts of the 64th Scientific Session of the American Diabetes Association. Florida, USA (June 2004) (Abstract 1417–P).
   Google Scholar
• WEBER AE, DOOSEOP K, BECONI M et al: MK-0431 Is a potent, selective, dipeptidyl peptidase IV inhibitor for the treatment of Type 2 diabetes. Program and abstracts of the 64th Scientific Session of the American Diabetes Association. Florida, USA (June 2004) (Abstract 633–P).
   Google Scholar
• HERMAN GA, ZHAO PL, DIETRICH B et al.: The DP-IV inhibitor MK-0431 enhances active GLP-1 and reduces glucose Following an OGTT in Type 2 diabetes. Program and abstracts of the 64th Scientific Session of the American Diabetes Association. Florida, USA (June 2004) (Abstract 353–P).
   Google Scholar
• HEINS J, GLUND K, HOFFMANN T et al: The DPP-IV-inhibitor P93/01 improves glucose tolerance in humans with HbA lc greater than 6.0. Program and abstracts of the 64th Scientific Session of the American Diabetes Association. Florida, USA (June 2004) (Abstract 539–P).
   Google Scholar
• JOSHI HV, NARAYANAN S, SHAH DM, BALASUBRAMANIAM G, VAKKALANKA KV: An orally active, highly specific dipeptidyl peptidase IV inhibitor exhibits potent activity in a murine OGTT model. Program and abstracts of the 64th Scientific Session of the American Diabetes Association. Florida, USA (June 2004) (Abstract 2379–P0).
   Google Scholar
• McNAMARA P, CARNEY D, HOLLIS C et al: PHX1004: A potent, orally efficacious dipeptidyl peptidase IV Inhibitor with antihyperglycemic properties. Program and abstracts of the 64th Scientific Session of the American Diabetes Association. Florida, USA (June 2004) (Abstract 2381–P0).
   Google Scholar
• TAKASAKI K, IWASE M, NAKAJIMA T et al: K579, a slow-binding inhibitor of dipeptidyl peptidase IV, is a long-acting hypoglycemic agent. Eur. Pharmacol (2004) 486(3):335–342.
   PubMed Web of Science ®Google Scholar
• TAKASAKI K, NAKAJIMA T, UENO K, NOMOTO Y, HIGO K: Effects of combination treatment with dipeptidyl peptidase IV inhibitor and sulfonylurea on glucose levels in rats. ./. Pharmacol Sci. (2004) 95(2):291–293.
   PubMed Web of Science ®Google Scholar
• TAKASAKI K, TAKADA H, NAKAJIMA T, UENO K, USHIKI J, HIGO K: Involvement of the active metabolites in the inhibitory activity of K579 on rat plasma dipeptidyl peptidase IV Eur..I. Pharmacol. (2004) 505(1–3):237–241.
   Google Scholar
• PLAMBOECK A, HOLST JJ, CARR RD, DEACON CF: Improvement of Glucose Tolerance by Neutral Endopeptidase Inhibition in Pigs. Program and abstracts of the 64th Scientific Session of the American 726 Expert Op/n. Investig. Drugs (2005) 14(6) Diabetes Association. Florida, USA (June 2004) (Abstract 2384–P0).
   Google Scholar
• TREBBIEN R, KLARSKOV L, OLESEN M, HOLST JJ, CARR RD, DEACON CF: Neutral endopeptidase 24.11 is important for the degradation of both endogenous and exogenous glucagon in anesthetized pigs. Am. J. Physic]. Endocrine]. Metab. (2004) 287(3):E431–E438.
   Google Scholar
• ARBIN V, CLAPERON N, FOURNIE-ZALUSKI MC, ROQUES BP, PEYROUX J: Effects of dual angiotensin-converting enzyme and neutral endopeptidase 24-11 chronic inhibition by mixanpril on insulin sensitivity in lean and obese Zucker rats. Cardiovasc. Pharmacy]. (2003) 41(2):254–264.
   PubMed Web of Science ®Google Scholar
• HENNEKENS CH, BURING JE: Epidemiology in Medicine. SL Mayrent (Ed.), Little, Brown, Boston, USA (1987) 1:186–189.
   Google Scholar