The GLP‐1 system as a therapeutic target

References

• Moore B., Edie E. S., Abram J. H. On the treatment of diabetes mellitus by the acid extraction of duodenal mucous membranes. Biochem J 1906; 1: 28–38
   PubMedGoogle Scholar
• Zunz E., La Barre J. Contributions a l'etude des variations physiologiques de la secretion interne du pancreas: relations entre les secretions externe et interne du pancreas. Arch Int Physiol Biochim Biophys 1929; 31: 20–44
   Google Scholar
• Mcintyre N., Holdsworth C. D., Turner D. S. New interpretation of oral glucose tolerance. Lancet 1964; 41: 20–1
   Google Scholar
• Perley M. J., Kipnis D. M. Plasma insulin responses to oral and intravenous glucose: studies in normal and diabetic subjects. J Clin Invest 1967; 46: 1954–62
   PubMed Web of Science ®Google Scholar
• Creutzfeldt W. The incretin concept today. Diabetologia 1979; 16: 75–85
   PubMed Web of Science ®Google Scholar
• Bell G. I., Sanchez‐Pescador R., Laybourn P. J., Najarian R. C. Exon duplication and divergence in the human preproglucagon gene. Nature 1983; 304: 368–71
   PubMed Web of Science ®Google Scholar
• Lopez L. C., Li W. H., Frazier M. L., Luo C. C., Saunders G. F. Evolution of glucagon genes. Mol Biol Evol 1984; 1: 335–44
   Google Scholar
• Kreymann B., Williams G., Ghatei M. A., Bloom S. R. Glucagon‐like peptide‐1 7‐36: a physiological incretin in man. Lancet 1987; 2: 1300–4
   PubMed Web of Science ®Google Scholar
• Nauck M. A., Heimesaat M. M., Orskov C., Holst J. J., 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: 301–7
   PubMed Web of Science ®Google Scholar
• Edwards C. M., Todd J. F., Mahmoudi M., Wang Z., Wang R. M., Ghatei M. A., 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: 86–93
   PubMed Web of Science ®Google Scholar
• Drucker D. J., Philippe J., Mojsov S., Chick W. L., Habener J. F. Glucagon‐like peptide 1 stimulates insulin gene expression and increases cyclic AMP levels in a rat islet cell line. Proc Natl Acad Sci U S A 1987; 84: 3434–8
   PubMed Web of Science ®Google Scholar
• De Leon D. D., Deng S., Madani R., Ahima R. S., Drucker D. J., Stoffers D. A. Role of endogenous glucagon‐like peptide‐1 in islet regeneration following partial pancreatectomy. Diabetes 2003; 52: 365–71
   PubMed Web of Science ®Google Scholar
• Wang Q., Brubaker P. L. Glucagon‐like peptide‐1 treatment delays the onset of diabetes in 8 week‐old db/db mice. Diabetologia 2002; 45: 1263–73
   PubMed Web of Science ®Google Scholar
• Farilla L., Bulotta A., Hirshberg B., Li Calzi S., Khoury N., Noushmehr H., et al. Glucagon‐like peptide 1 inhibits cell apoptosis and improves glucose responsiveness of freshly isolated human islets. Endocrinology 2003; 144: 5149–58
   PubMed Web of Science ®Google Scholar
• UK Prospective Diabetes Study (UKPDS) Group. Glycemic control with diet, sulfonylurea, metformin, or insulin in patients with type 2 diabetes mellitus: progressive requirement for multiple therapies (UKPDS 49). JAMA 1999; 281: 2005–12
   Google Scholar
• Gutniak M., Orskov C., Holst J. J., 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: 1316–22
   PubMed Web of Science ®Google Scholar
• Unger R. H. Role of glucagon in the pathogenesis of diabetes: the status of the controversy. Metabolism 1978; 27: 1691–709
   PubMed Web of Science ®Google Scholar
• Unger R. H., Orci L. The essential role of glucagon in the pathogenesis of diabetes mellitus. Lancet 1975; 7897: 14–6
   Google Scholar
• Wettergren A., Schjoldager B., Mortensen P. E., Myhre J., Christiansen J., Holst J. J. Truncated GLP‐1 (proglucagon 78‐107‐amide) inhibits gastric and pancreatic functions in man. Dig Dis Sci 1993; 38: 665–73
   PubMed Web of Science ®Google Scholar
• Nauck M. A., Niedereichholz U., Ettler R., Holst J. J., Orskov C., Ritzel R., et al. Glucagon‐like peptide 1 inhibition of gastric emptying outweighs its insulinotropic effects in healthy humans. Am J Physiol 1997; 273: E981–8
   PubMed Web of Science ®Google Scholar
• Naslund E., Gutniak M., Skogar S., Rossner S., Hellstrom P. M. Glucagon‐like peptide 1 increases the period of postprandial satiety and slows gastric emptying in obese men. Am J Clin Nutr 1998; 68: 525–30
   PubMed Web of Science ®Google Scholar
• Turton M. D., O'Shea D., Gunn I., Beak S. A., Edwards C. M., Meeran K., et al. A role for glucagon‐like peptide‐1 in the central regulation of feeding. Nature 1996; 379: 69–72
   PubMed Web of Science ®Google Scholar
• Meeran K., O'Shea D., Edwards C. M., Turton M. D., Heath M. M., Gunn I., et al. Repeated intracerebroventricular administration of glucagon‐like peptide‐1‐(7‐36) amide or exendin‐(9‐39) alters body weight in the rat. Endocrinology 1999; 140: 244–50
   PubMed Web of Science ®Google Scholar
• Flint A., Raben A., Astrup A., Holst J. J. Glucagon‐like peptide 1 promotes satiety and suppresses energy intake in humans. J Clin Invest 1998; 101: 515–20
   PubMed Web of Science ®Google Scholar
• Gutzwiller J. P., Drewe J., Goke B., Schmidt H., Rohrer B., Lareida J., et al. Glucagon‐like peptide‐1 promotes satiety and reduces food intake in patients with diabetes mellitus type 2. Am J Physiol 1999; 276: R1541–4
   PubMed Web of Science ®Google Scholar
• D'Alessio D. A., Kahn S. E., Leusner C. R., Ensinck J. W. Glucagon‐like peptide 1 enhances glucose tolerance both by stimulation of insulin release and by increasing insulin‐independent glucose disposal. J Clin Invest 1994; 93: 2263–6
   PubMed Web of Science ®Google Scholar
• Orskov L., Holst J. J., Moller J., Orskov C., Moller N., Alberti K. G., et al. GLP‐1 does not not acutely affect insulin sensitivity in healthy man. Diabetologia 1996; 39: 1227–32
   PubMed Web of Science ®Google Scholar
• Ahrén B., Larsson H., Holst J. J. Effects of glucagon‐like peptide‐1 on islet function and insulin sensitivity in noninsulin‐dependent diabetes mellitus. J Clin Endocrinol Metab 1997; 82: 473–8
   PubMed Web of Science ®Google Scholar
• Holz G. G 4th., Kuhtreiber W. M., Habener J. F. Pancreatic beta‐cells are rendered glucose‐competent by the insulinotropic hormone glucagon‐like peptide‐1(7‐37). Nature 1993; 361: 362–5
   PubMed Web of Science ®Google Scholar
• Ritzel R., Orskov C., Holst J. J., Nauck M. A. Pharmacokinetic, insulinotropic, and glucagonostatic properties of GLP‐1 [7‐36 amide] after subcutaneous injection in healthy volunteers. Dose‐response‐relationships. Diabetologia 1995; 38: 720–5
   PubMed Web of Science ®Google Scholar
• Qualmann C., Nauck M. A., Holst J. J., Orskov C., Creutzfeldt W. Insulinotropic actions of intravenous glucagon‐like peptide‐1 (GLP‐1) [7‐36 amide] in the fasting state in healthy subjects. Acta Diabetol 1995; 32: 13–6
   PubMed Web of Science ®Google Scholar
• Knop F. K., Vilsboll T., Larsen S., Madsbad S., Holst J. J., Krarup T. No hypoglycemia after subcutaneous administration of glucagon‐like peptide‐1 in lean type 2 diabetic patients and in patients with diabetes secondary to chronic pancreatitis. Diabetes Care 2003; 26: 2581–7
   PubMed Web of Science ®Google Scholar
• Toft‐Nielsen M., Madsbad S., Holst J. J. Exaggerated secretion of glucagon‐like peptide‐1 (GLP‐1) could cause reactive hypoglycaemia. Diabetologia 1998; 41: 1180–6
   Google Scholar
• Edwards C. M., Todd J. F., Ghatei M. A., Bloom S. R. Subcutaneous glucagon‐like peptide‐1 (7‐36) amide is insulinotropic and can cause hypoglycaemia in fasted healthy subjects. Clin Sci 1998; 95: 719–24
   Google Scholar
• Vilsboll T., Krarup T., Madsbad S., Holst J. J. No reactive hypoglycaemia in Type 2 diabetic patients after subcutaneous administration of GLP‐1 and intravenous glucose. Diabet Med 2001; 18: 144–9
   PubMed Web of Science ®Google Scholar
• UK Prospective Diabetes Study (UKPDS) Group. Intensive blood‐glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet 1998; 352: 837–53
   PubMed Web of Science ®Google Scholar
• Barragan J. M., Rodriguez R. E., Blazquez E. Changes in arterial blood pressure and heart rate induced by glucagon‐like peptide‐1‐(7‐36) amide in rats. Am J Physiol 1994; 266: E459–66
   Google Scholar
• Yu M., Moreno C., Hoagland K. M., Dahly A., Ditter K., Mistry M., et al. Antihypertensive effect of glucagon‐like peptide 1 in Dahl salt‐sensitive rats. J Hypertens 2003; 21: 1125–35
   PubMed Web of Science ®Google Scholar
• Gros R., You X., Baggio L. L., Kabir M. G., Sadi A. M., Mungrue I. N., et al. Cardiac function in mice lacking the glucagon‐like peptide‐1 receptor. Endocrinology 2003; 144: 2242–52
   PubMed Web of Science ®Google Scholar
• Edwards C. M., Edwards A. V., Bloom S. R. Cardiovascular and pancreatic endocrine responses to glucagon‐like peptide‐1(7‐36) amide in the conscious calf. Exp Physiol 1997; 82: 709–16
   PubMedGoogle Scholar
• Nikolaidis L. A., Doverspike A., Hentosz T., Zourelias L., Shen Y. T., Elahi D., et al. Glucagon‐like peptide‐1 limits myocardial stunning following brief coronary occlusion and reperfusion in conscious canines. J Pharmacol Exp Ther 2005; 312: 303–8
   PubMed Web of Science ®Google Scholar
• Nystrom T., Gutniak M. K., Zhang Q., Zhang F., Holst J. J., Ahren B., et al. Effects of glucagon‐like peptide‐1 on endothelial function in type 2 diabetes patients with stable coronary artery disease. Am J Physiol Endocrinol Metab 2004; 287: E1209–15
   PubMedGoogle Scholar
• Nikolaidis L. A., Mankad S., Sokos G. G., Miske G., Shah A., Elahi D., et al. Effects of glucagon‐like peptide‐1 in patients with acute myocardial infarction and left ventricular dysfunction after successful reperfusion. Circulation 2004; 109: 962–5
   PubMed Web of Science ®Google Scholar
• Tang‐Christensen M., Larsen P. J., Goke R., Fink‐Jensen A., Jessop D. S., Moller M., et al. Central administration of GLP‐1‐(7‐36) amide inhibits food and water intake in rats. Am J Physiol 1996; 271: R848–56
   PubMed Web of Science ®Google Scholar
• Tang‐Christensen M., Vrang N., Larsen P. J. Glucagon‐like peptide 1(7‐36) amide's central inhibition of feeding and peripheral inhibition of drinking are abolished by neonatal monosodium glutamate treatment. Diabetes 1998; 47: 530–7
   PubMedGoogle Scholar
• Yamamoto H., Kishi T., Lee C. E., Choi B. J., Fang H., Hollenberg A. N., et al. Glucagon‐like peptide‐1‐responsive catecholamine neurons in the area postrema link peripheral glucagon‐like peptide‐1 with central autonomic control sites. J Neurosci 2003; 23: 2939–46
   PubMed Web of Science ®Google Scholar
• Gutzwiller J. P., Goke B., Drewe J., Hildebrand P., Ketterer S., Handschin D., et al. Glucagon‐like peptide‐1: a potent regulator of food intake in humans. Gut 1999; 44: 81–6
   PubMed Web of Science ®Google Scholar
• Gutzwiller J. P., Tschopp S., Bock A., Zehnder C. E., Huber A. R., Kreyenbuehl M., et al. Glucagon‐like peptide 1 induces natriuresis in healthy subjects and in insulin‐resistant obese men. J Clin Endocrinol Metab 2004; 89: 3055–61
   PubMed Web of Science ®Google Scholar
• Perry T., Haughey N. J., Mattson M. P., Egan J. M., Greig N. H. Protection and reversal of excitotoxic neuronal damage by glucagon‐like peptide‐1 and exendin‐4. J Pharmacol Exp Ther 2002; 302: 881–8
   PubMed Web of Science ®Google Scholar
• Perry T., Lahiri D. K., Sambamurti K., Chen D., Mattson M. P., Egan J. M., et al. Glucagon‐like peptide‐1 decreases endogenous amyloid‐beta peptide (Abeta) levels and protects hippocampal neurons from death induced by Abeta and iron. J Neurosci Res 2003; 72: 603–12
   PubMed Web of Science ®Google Scholar
• During M. J., Cao L., Zuzga D. S., Francis J. S., Fitzsimons H. L., Jiao X., et al. Glucagon‐like peptide‐1 receptor is involved in learning and neuroprotection. Nat Med 2003; 9: 1173–9
   PubMed Web of Science ®Google Scholar
• Deacon C. F., Knudsen L. B., Madsen K., Wiberg F. C., Jacobsen O., Holst J. J. Dipeptidyl peptidase IV resistant analogues of glucagon‐like peptide‐1 which have extended metabolic stability and improved biological activity. Diabetologia 1998; 41: 271–8
   PubMed Web of Science ®Google Scholar
• Nauck M. A., Kleine N., Orskov C., Holst J. J., Willms B., Creutzfeldt W. Normalization of fasting hyperglycaemia by exogenous glucagon‐like peptide 1 (7‐36 amide) in type 2 (non‐insulin‐dependent) diabetic patients. Diabetologia 1993; 36: 741–4
   PubMed Web of Science ®Google Scholar
• Todd J. F., Edwards C. M., Ghatei M. A., Mather H. M., Bloom S. R. Subcutaneous glucagon‐like peptide‐1 improves postprandial glycaemic control over a 3‐week period in patients with early type 2 diabetes. Clin Sci 1998; 95: 325–9
   Web of Science ®Google Scholar
• Gutniak M. K., Larsson H., Sanders S. W., Juneskans O., Holst J. J., Ahren B. GLP‐1 tablet in type 2 diabetes in fasting and postprandial conditions. Diabetes Care 1997; 20: 1874–9
   PubMed Web of Science ®Google Scholar
• Zander M., Taskiran M., Toft‐Nielsen M. B., Madsbad S., Holst J. J. Additive glucose‐lowering effects of glucagon‐like peptide‐1 and metformin in type 2 diabetes. Diabetes Care 2001; 24: 720–5
   PubMed Web of Science ®Google Scholar
• Zander M., Madsbad S., Madsen J. L., Holst J. J. Effect of 6‐week course of glucagon‐like peptide 1 on glycaemic control, insulin sensitivity, and beta‐cell function in type 2 diabetes: a parallel‐group study. Lancet 2002; 359: 824–30
   PubMed Web of Science ®Google Scholar
• Meneilly G. S., Greig N., Tildesley H., Habener J. F., Egan J. M., 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: 2835–41
   PubMed Web of Science ®Google Scholar
• Zander M., Christiansen A., Madsbad S., Holst J. J. Additive effects of glucagon‐like peptide 1 and pioglitazone in patients with type 2 diabetes. Diabetes Care 2004; 27: 1910–4
   PubMed Web of Science ®Google Scholar
• Raufman J. P., Singh L., Singh G., Eng J. Truncated glucagon‐like peptide‐1 interacts with exendin receptors on dispersed acini from guinea pig pancreas. Identification of a mammalian analogue of the reptilian peptide exendin‐4. J Biol Chem 1992; 267: 21432–7
   PubMed Web of Science ®Google Scholar
• Edwards C. M., Stanley S. A., Davis R., Brynes A. E., Frost G. S., Seal L. J., et al. Exendin‐4 reduces fasting and postprandial glucose and decreases energy intake in healthy volunteers. Am J Physiol Endocrinol Metab 2001; 281: E155–61
   PubMed Web of Science ®Google Scholar
• Greig N. H., Holloway H. W., De Ore K. A., Jani D., Wang Y., Zhou J., et al. Once daily injection of exendin‐4 to diabetic mice achieves long‐term beneficial effects on blood glucose concentrations. Diabetologia 1999; 42: 45–50
   PubMed Web of Science ®Google Scholar
• Young A. A., Gedulin B. R., Bhavsar S., Bodkin N., Jodka C., Hansen B., et al. Glucose‐lowering and insulin‐sensitizing actions of exendin‐4: studies in obese diabetic (ob/ob, db/db) mice, diabetic fatty Zucker rats, and diabetic rhesus monkeys (Macaca mulatta). Diabetes 1999; 48: 1026–34
   PubMed Web of Science ®Google Scholar
• Xu G., Stoffers D. A., Habener J. F., Bonner‐Weir S. Exendin‐4 stimulates both beta‐cell replication and neogenesis, resulting in increased beta‐cell mass and improved glucose tolerance in diabetic rats. Diabetes 1999; 48: 2270–6
   PubMed Web of Science ®Google Scholar
• Tourrel C., Bailbe D., Meile M. J., Kergoat M., Portha B. Glucagon‐like peptide‐1 and exendin‐4 stimulate beta‐cell neogenesis in streptozotocin‐treated newborn rats resulting in persistently improved glucose homeostasis at adult age. Diabetes 2001; 50: 1562–70
   PubMed Web of Science ®Google Scholar
• Szayna M., Doyle M. E., Betkey J. A., Holloway H. W., Spencer R. G., Greig N. H., et al. Exendin‐4 decelerates food intake, weight gain, and fat deposition in Zucker rats. Endocrinology 2000; 141: 1936–41
   PubMed Web of Science ®Google Scholar
• Egan J. M., Clocquet A. R., Elahi D. The insulinotropic effect of acute exendin‐4 administered to humans: comparison of nondiabetic state to type 2 diabetes. J Clin Endocrinol Metab 2002; 87: 1282–90
   PubMed Web of Science ®Google Scholar
• Kolterman O. G., Buse J. B., Fineman M. S., Gaines E., Heintz S., Bicsak T. A., et al. Synthetic exendin‐4 (exenatide) significantly reduces postprandial and fasting plasma glucose in subjects with type 2 diabetes. J Clin Endocrinol Metab 2003; 88: 3082–9
   PubMed Web of Science ®Google Scholar
• Dupre J., Behme M. T., McDonald T. J. Exendin‐4 normalized postcibal glycemic excursions in type 1 diabetes. J Clin Endocrinol Metab 2004; 89: 3469–73
   PubMed Web of Science ®Google Scholar
• Egan J. M., Meneilly G. S., Elahi D. Effects of 1‐mo bolus subcutaneous administration of exendin‐4 in type 2 diabetes. Am J Physiol Endocrinol Metab 2003; 284: E1072–9
   PubMed Web of Science ®Google Scholar
• Fineman M. S., Bicsak T. A., Shen L. Z., Taylor K., Gaines E., Varns A., et al. Effect on glycemic control of exenatide (synthetic exendin‐4) additive to existing metformin and/or sulfonylurea treatment in patients with type 2 diabetes. Diabetes Care 2003; 26: 2370–7
   PubMed Web of Science ®Google Scholar
• Fineman M. S., Shen L. Z., Taylor K., Kim D. D., Baron A. D. 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: 411–7
   PubMed Web of Science ®Google Scholar
• Buse J. B., Henry R. R., Han J., Kim D. D., Fineman M. S., 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: 2628–35
   PubMed Web of Science ®Google Scholar
• Knudsen L. B., Nielsen P. F., Huusfeldt P. O., Johansen N. L., Madsen K., Pedersen F. Z., et al. Potent derivatives of glucagon‐like peptide‐1 with pharmacokinetic properties suitable for once daily administration. J Med Chem 2000; 43: 1664–9
   PubMed Web of Science ®Google Scholar
• Larsen P. J., Fledelius C., Knudsen L. B., Tang‐Christensen M. Systemic administration of the long‐acting GLP‐1 derivative NN2211 induces lasting and reversible weight loss in both normal and obese rats. Diabetes 2001; 50: 2530–9
   PubMed Web of Science ®Google Scholar
• Sturis J., Gotfredsen C. F., Romer J., Rolin B., Ribel U., Brand C. L., et al. GLP‐1 derivative liraglutide in rats with beta‐cell deficiencies: influence of metabolic state on beta‐cell mass dynamics. Br J Pharmacol 2003; 140: 123–32
   PubMed Web of Science ®Google Scholar
• Bock T., Pakkenberg B., Buschard K. The endocrine pancreas in non‐diabetic rats after short‐term and long‐term treatment with the long‐acting GLP‐1 derivative NN2211. APMIS 2003; 111: 1117–24
   PubMed Web of Science ®Google Scholar
• Rolin B., Larsen M. O., Gotfredsen C. F., Deacon C. F., Carr R. D., Wilken M., et al. The long‐acting GLP‐1 derivative NN2211 ameliorates glycemia and increases beta‐cell mass in diabetic mice. Am J Physiol Endocrinol Metab 2002; 283: E745–52
   PubMed Web of Science ®Google Scholar
• Ribel U., Larsen M. O., Rolin B., Carr R. D., Wilken M., Sturis J., et al. NN2211: a long‐acting glucagon‐like peptide‐1 derivative with anti‐diabetic effects in glucose‐intolerant pigs. Eur J Pharmacol 2002; 451: 217–25
   PubMed Web of Science ®Google Scholar
• Elbrond B., Jakobsen G., Larsen S., Agerso H., Jensen L. B., Rolan P., et al. Pharmacokinetics, pharmacodynamics, safety, and tolerability of a single‐dose of NN2211, a long‐acting glucagon‐like peptide 1 derivative, in healthy male subjects. Diabetes Care 2002; 25: 1398–404
   PubMed Web of Science ®Google Scholar
• Juhl C. B., Hollingdal M., Sturis J., Jakobsen G., Agerso H., Veldhuis J., et al. Bedtime administration of NN2211, a long‐acting GLP‐1 derivative, substantially reduces fasting and postprandial glycemia in type 2 diabetes. Diabetes 2002; 51: 424–9
   PubMed Web of Science ®Google Scholar
• Degn K. B., Juhl C. B., Sturis J., Jakobsen G., Brock B., Chandramouli V., et al. One week's treatment with the long‐acting glucagon‐like peptide 1 derivative liraglutide (NN2211) markedly improves 24‐h glycemia and alpha‐ and beta‐cell function and reduces endogenous glucose release in patients with type 2 diabetes. Diabetes 2004; 53: 1187–94
   PubMed Web of Science ®Google Scholar
• Edwards C. M., Bloom S. R. The incretins‐outdated terminology in man?. Diabetologia 1999; 42: 1148–9
   Google Scholar
• Harder H., Nielsen L., Tu D. T., 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: 1915–21
   PubMed Web of Science ®Google Scholar
• Madsbad S., Schmitz O., Ranstam J., Jakobsen G., Matthews D. R., NN2211‐1310 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 (NN2211): a 12‐week, double‐blind, randomized, controlled trial. Diabetes Care 2004; 27: 1335–42
   PubMed Web of Science ®Google Scholar
• UK Prospective Diabetes Study (UKPDS) Group. Effect of intensive blood‐glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet 1998; 352: 854–65
   PubMed Web of Science ®Google Scholar
• Green B. D., Gault V. A., O'harte F. P., Flatt P. R. Structurally modified analogues of glucagon‐like peptide‐1 (GLP‐1) and glucose‐dependent insulinotropic polypeptide (GIP) as future antidiabetic agents. Curr Pharm Des 2004; 10: 3651–62
   PubMed Web of Science ®Google Scholar
• Kim J. G., Baggio L. L., Bridon D. P., Castaigne J. P., Robitaille M. F., Jette L., 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: 751–9
   PubMed Web of Science ®Google Scholar
• Baggio L. L., Huang Q., Brown T. J., Drucker D. J. 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: 2492–500
   PubMed Web of Science ®Google Scholar
• Marguet D., Baggio L., Kobayashi T., Bernard A. M., Pierres M., Nielsen P. F., et al. Enhanced insulin secretion and improved glucose tolerance in mice lacking CD26. Proc Natl Acad Sci U S A 2000; 97: 6874–9
   PubMed Web of Science ®Google Scholar
• Conarello S. L., Li Z., Ronan J., Roy R. S., Zhu L., Jiang G., et al. Mice lacking dipeptidyl peptidase IV are protected against obesity and insulin resistance. Proc Natl Acad Sci U S A 2003; 100: 6825–30
   PubMed Web of Science ®Google Scholar
• Mentlein R., Gallwitz B., Schmidt W. E. 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 J Biochem 1993; 214: 829–35
   PubMedGoogle Scholar
• Hansotia T., Baggio L. L., Delmeire D., Hinke S. A., Yamada Y., Tsukiyama K., 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: 1326–35
   PubMed Web of Science ®Google Scholar
• Bauvois B., Sanceau J., Wietzerbin J. Human U937 cell surface peptidase activities: characterization and degradative effect on tumor necrosis factor‐alpha. Eur J Immunol 1992; 22: 923–30
   PubMed Web of Science ®Google Scholar
• Maes M., De Meester I., Scharpe S., Desnyder R., Ranjan R., Meltzer H. Y. Alterations in plasma dipeptidyl peptidase IV enzyme activity in depression and schizophrenia: effects of antidepressants and antipsychotic drugs. Acta Psychiatr Scand 1996; 93: 1–8
   Google Scholar
• Darmoul D., Lacasa M., Chantret I., Swallow D. M., Trugnan G. Isolation of a cDNA probe for the human intestinal dipeptidylpeptidase IV and assignment of the gene locus DPP4 to chromosome 2. Ann Hum Genet 1990; 54: 191–7
   Google Scholar
• Hildebrandt M., Reutter W., Arck P., Rose M., Klapp B. F. A guardian angel: the involvement of dipeptidyl peptidase IV in psychoneuroendocrine function, nutrition and immune defence. Clin Sci 2000; 99: 93–104
   PubMed Web of Science ®Google Scholar
• Reimer M. K., Holst J. J., Ahren B. Long‐term inhibition of dipeptidyl peptidase IV improves glucose tolerance and preserves islet function in mice. Eur J Endocrinol 2002; 146: 717–27
   PubMed Web of Science ®Google Scholar
• Sudre B., Broqua P., White R. B., Ashworth D., Evans D. M., Haigh R., et al. Chronic inhibition of circulating dipeptidyl peptidase IV by FE 999011 delays the occurrence of diabetes in male zucker diabetic fatty rats. Diabetes 2002; 51: 1461–9
   PubMed Web of Science ®Google Scholar
• Pospisilik J. A., Stafford S. G., Demuth H. U., Brownsey R., Parkhouse W., Finegood D. T., et al. Long‐term treatment with the dipeptidyl peptidase IV inhibitor P32/98 causes sustained improvements in glucose tolerance, insulin sensitivity, hyperinsulinemia, and beta‐cell glucose responsiveness in VDF (fa/fa) Zucker rats. Diabetes 2002; 51: 943–50
   PubMed Web of Science ®Google Scholar
• Ahren B., Simonsson E., Larsson H., Landin‐Olsson M., Torgeirsson H., Jansson P. A., et al. Inhibition of dipeptidyl peptidase IV improves metabolic control over a 4‐week study period in type 2 diabetes. Diabetes Care 2002; 25: 869–75
   PubMed Web of Science ®Google Scholar
• Ahren B., Landin‐Olsson M., Jansson P. A., Svensson M., Holmes D., Schweizer A. Inhibition of dipeptidyl peptidase‐4 reduces glycemia, sustains insulin levels, and reduces glucagon levels in type 2 diabetes. J Clin Endocrinol Metab 2004; 89: 2078–84
   PubMed Web of Science ®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: 2874–80
   PubMed Web of Science ®Google Scholar