Targeting the intestinal L-cell for obesity and type 2 diabetes treatment

References

• Malik VS, Willett WC, Hu FB. Global obesity: trends, risk factors and policy implications. Nat. Rev. Endocrinol. 9(1), 13–27 (2013).
   PubMed Web of Science ®Google Scholar
• Ryan D, Bray G. Pharmacologic treatment options for obesity: what is old is new again. Curr. Hypertens. Rep. 15(3), 182–189 (2013).
   Google Scholar
• Diana R, Raj P, Stephanie KL, Cintia C, David CWL. Long term pharmacotherapy for obesity and overweight: updated meta-analysis. BMJ 335, 1194 (2007).
   Google Scholar
• Kirk SFL, Penney TL, McHugh TL, Sharma AM. Effective weight management practice: a review of the lifestyle intervention evidence. Int. J. Obes. 36(2), 178–185 (2012).
   Web of Science ®Google Scholar
• Colquitt JL, Picot J, Loveman E, Clegg AJ. Surgery for obesity. Cochrane Database Syst. Rev. (2), CD003641 (2009).
   Google Scholar
• DeFronzo RA, Abdul-Ghani MA. Preservation of beta-cell function: the key to diabetes prevention. J. Clin. Endocrinol. Metab. 96(8), 2354–2366 (2011).
   PubMed Web of Science ®Google Scholar
• DeFronzo RA. Overview of newer agents: where treatment is going. Am. J. Med. 123(3 Suppl.), S38–S48 (2010).
   PubMed Web of Science ®Google Scholar
• Grunberger G. Novel therapies for management of type 2 diabetes mellitus part 2 – addressing the incretin defect in clinical setting in 2013. J. Diabetes 5(3), 241–253 (2013).
   Google Scholar
• Egerod KL, Engelstoft MS, Grunddal KV et al. A major lineage of enteroendocrine cells coexpress CCK, secretin, GIP, GLP-1, PYY, and neurotensin but not somatostatin. Endocrinology 153(12), 5782–5795 (2012).
   Google Scholar
• Habib AM, Richards P, Rogers GJ, Reimann F, Gribble FM. Co-localisation and secretion of glucagon-like peptide 1 and peptide YY from primary cultured human L cells. Diabetologia 56(6), 1413–1416 (2013).
   PubMed Web of Science ®Google Scholar
• Habib AM, Richards P, Cairns LS et al. Overlap of endocrine hormone expression in the mouse intestine revealed by transcriptional profiling and flow cytometry. Endocrinology 153(7), 3054–3065 (2012).
   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. Pep. 114(2G), 189–196 (2003).
   Google Scholar
• Holst JJ. Incretin hormones and the satiation signal. Int. J. Obes. 37(9), 1161–1168 (2013).
   PubMed Web of Science ®Google Scholar
• Holst JJ. The physiology of glucagon-like peptide 1. Physiol. Rev. 87(4), 1409–1439 (2007).
   PubMed Web of Science ®Google Scholar
• Baldissera FG, Holst JJ, Knuhtsen S, Hilsted L, Nielsen OV. Oxyntomodulin (glicentin-(33-69)): pharmacokinetics, binding to liver cell membranes, effects on isolated perfused pig pancreas, and secretion from isolated perfused lower small intestine of pigs. Regul. Pept. 21(1–2), 151–166 (1988).
   PubMed Web of Science ®Google Scholar
• Pedersen J, Ugleholdt RK, Jorgensen SM et al. Glucose metabolism is altered after loss of L cells and alfa cells but not influenced by loss of K cells. Am. J. Physio. Endocrinol. Metab. 304(1), e60–e73 (2013).
   Google Scholar
• Gibbs J, Young RC, Smith GP. Cholecystokinin decreases food intake in rats. J. Compar. Physiol. Psychol. 84(3), 488–495 (1973).
   PubMedGoogle Scholar
• Suzuki K, Jayasena CN, Bloom SR. Obesity and appetite control. Exp. Diabetes Res. 2012, 824305 (2012).
   PubMedGoogle Scholar
• Amitani M, Asakawa A, Amitani H, Inui A. The role of leptin in the control of insulin-glucose axis. Front. Neurosci. 7, 51 (2013).
   PubMed Web of Science ®Google Scholar
• Suzuki K, Simpson KA, Minnion JS, Shillito JC, Bloom SR. The role of gut hormones and the hypothalamus in appetite regulation. Endocr. J. 57(5), 359–372 (2010).
   PubMed Web of Science ®Google Scholar
• Sumithran P, Proietto J. The defence of body weight: a physiological basis for weight regain after weight loss. Clin. Sci. (Lond.) 124(4), 231–241 (2013).
   PubMed Web of Science ®Google Scholar
• Chaudhri OB, Salem V, Murphy KG, Bloom SR. Gastrointestinal satiety signals. Ann. Rev. Physiol. 70, 239–255 (2008).
   PubMed Web of Science ®Google Scholar
• Wang C, Bomberg E, Billington CJ, Levine AS, Kotz CM. Brain-derived neurotrophic factor (BDNF) in the hypothalamic ventromedial nucleus increases energy expenditure. Brain Res. 1336, 66–77 (2010).
   PubMed Web of Science ®Google Scholar
• Jo YH, Chua S Jr. Transcription factors in the development of medial hypothalamic structures. Am. J. Physiol. Endocrinol. Metab. 297(3), e563–e567 (2009).
   Google Scholar
• Murphy KG, Bloom SR. Gut hormones and the regulation of energy homeostasis. Nature 444(7121), 854–859 (2006).
   PubMed Web of Science ®Google Scholar
• Alhadeff AL, Rupprecht LE, Hayes MR. GLP-1 Neurons in the nucleus of the solitary tract project directly to the ventral tegmental area and nucleus accumbens to control for food intake. Endocrinology 153(2), 647–658 (2012).
   PubMed Web of Science ®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 140(11), 5356–5363 (1999).
   PubMed Web of Science ®Google Scholar
• Hjollund KR, Deacon CF, Holst JJ. Dipeptidyl peptidase-4 inhibition increases portal concentrations of intact glucagon-like peptide-1 (GLP-1) to a greater extent than peripheral concentrations in anaesthetised pigs. Diabetologia 54(8), 2206–2208 (2011).
   PubMed Web of Science ®Google Scholar
• Ruttimann EB, Arnold M, Hillebrand JJ, Geary N, Langhans W. Intrameal hepatic portal and intraperitoneal infusions of glucagon-like peptide-1 reduce spontaneous meal size in the rat via different mechanisms. Endocrinology 150(3), 1174–1181 (2009).
   PubMed Web of Science ®Google Scholar
• Abbott CR, Monteiro M, Small CJ et al. The inhibitory effects of peripheral administration of peptide YY(3-36) and glucagon-like peptide-1 on food intake are attenuated by ablation of the vagal-brainstem-hypothalamic pathway. Brain Res. 1044(1), 127–131 (2005).
   PubMed Web of Science ®Google Scholar
• Bucinskaite V, Tolessa T, Pedersen J et al. Receptor-mediated activation of gastric vagal afferents by glucagon-like peptide-1 in the rat. Neurogastroenterol. Motil. 21(9), 978–e78 (2009).
   PubMed Web of Science ®Google Scholar
• Moran TH, Baldessarini AR, Salorio CF, Lowery T, Schwartz GJ. Vagal afferent and efferent contributions to the inhibition of food intake by cholecystokinin. Am. J. Physiol. 272(4), R1245–R1251 (1997).
   Google Scholar
• Koda S, Date Y, Murakami N et al. The role of the vagal nerve in peripheral PYY3-36 induced feeding reduction in rats. Endocrinology 146(5), 2369–2375 (2005).
   Google Scholar
• Plamboeck A, Veedfald S, Deacon CF et al. The effect of exogenous GLP-1 on food intake is lost in male truncally vagotomized subjects with pyloroplasty. Am. J. Physiol. Gastrointest. Liver Physiol. 304(12), G1117–G1127 (2013).
   PubMed Web of Science ®Google Scholar
• Nakagawa A, Satake H, Nakabayashi H et al. Receptor gene expression of glucagon-like peptide-1, but not glucose-dependent insulinotropic polypeptide, in rat nodose ganglion cells. Auton. Neurosci. 110(1), 36–43 (2004).
   PubMed Web of Science ®Google Scholar
• Vahl TP, Tauchi M, Durler TS et al. Glucagon-like peptide-1 (GLP-1) receptors expressed on nerve terminals in the portal vein mediate the effects of endogenous GLP-1 on glucose tolerance in rats. Endocrinology 148(10), 4965–4973 (2007).
   Google Scholar
• Liu WY, Wang ZB, Zhang LC, Wei X, Li L. Tight junction in blood-brain barrier: an overview of structure, regulation, and regulator substances. CNS Neurosci. Ther. 18(8), 609–615 (2012).
   PubMed Web of Science ®Google Scholar
• Fry M, Ferguson AV. The sensory circumventricular organs: Brain targets for circulating signals controlling ingestive behavior. Physiol. Behav. 91(4), 413–423 (2007).
   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 45(6), 832–835 (1996).
   PubMed Web of Science ®Google Scholar
• Kastin A, Akerstrom V, Pan W. Interactions of glucagon-like peptide-1 (GLP-1) with the blood-brain barrier. J. Mol. Neurosci. 18(1–2), 7–14 (2002).
   PubMed Web of Science ®Google Scholar
• Williams DL, Baskin DG, Schwartz MW. Evidence that intestinal glucagon-like peptide-1 plays a physiological role in satiety. Endocrinology 150(4), 1680–1687 (2009).
   PubMed Web of Science ®Google Scholar
• Flint A, Raben A, Astrup A, Holst JJ. Glucagon-like peptide 1 promotes satiety and suppresses energy intake in humans. J. Clin. Invest. 101(3), 515–520 (1998).
   PubMed Web of Science ®Google Scholar
• Degen L, Oesch S, Casanova M et al. Effect of peptide YY 3–36 on food intake in humans. Gastroenterology 129(5), 1430–1436 (2005).
   PubMed Web of Science ®Google Scholar
• Lieverse RJ, Jansen JB, Masclee AA, Lamers CB. Satiety effects of a physiological dose of cholecystokinin in humans. Gut 36(2), 176–179 (1995).
   PubMed Web of Science ®Google Scholar
• Baraboi ED, Smith P, Ferguson AV, Richard D. Lesions of area postrema and subfornical organ alter exendin-4-induced brain activation without preventing the hypophagic effect of the GLP-1 receptor agonist. Am. J. Physiol. Regul. Integr. Comp. Physiol. 298(4), R1098–R1110 (2010).
   Google Scholar
• le Roux CW, Welbourn R, Werling M et al. Gut hormones as mediators of appetite and weight loss after roux-en-Y gastric bypass. Ann. Surg. 246(5), 780–785 (2007).
   PubMed Web of Science ®Google Scholar
• Dirksen C, Jorgensen NB, Bojsen-Moller KN et al. Gut hormones, early dumping and resting energy expenditure in patients with good and poor weight loss response after Roux-en-Y gastric bypass. Int. J. Obes. (Lond.) doi:10.1038/ijo.2013.15 (2013) ( Epub ahead of print).
   Google Scholar
• Rehfeld JF, Agersnap M. Unsulfated cholecystokinin: an overlooked hormone? Regul. Pept. 173(1–3), 1–5 (2012).
   Google Scholar
• Wank SA, Pisegna JR, de WA. Brain and gastrointestinal cholecystokinin receptor family: structure and functional expression. Proc. Natl Acad. Sci. USA 89(18), 8691–8695 (1992).
   PubMed Web of Science ®Google Scholar
• Deacon CF, Knudsen LB, Madsen K, Wiberg FC, Jacobsen O, Holst JJ. Dipeptidyl peptidase IV resistant analogues of glucagon-like peptide-1 which have extended metabolic stability and improved biological activity. Diabetologia 41(3), 271–278 (1998).
   PubMed Web of Science ®Google Scholar
• Deacon CF, 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. Clin. Endocrinol. Metab. 80(3), 952–957 (1995).
   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. J. Clin. Endocrinol. Metab. 63(2), 492–498 (1986).
   PubMed Web of Science ®Google Scholar
• Holst JJ, Knop FK, Vilsboll T, Krarup T, Madsbad S. Loss of incretin effect is a specific, important, and early characteristic of type 2 diabetes. Diabetes Care 34( Suppl. 2), S251–S257 (2011).
   PubMed Web of Science ®Google Scholar
• Heer J, Rasmussen C, Coy DH, Holst JJ. Glucagon-like peptide-1, but not glucose-dependent insulinotropic peptide, inhibits glucagon secretion via somatostatin (receptor subtype 2) in the perfused rat pancreas. Diabetologia 51(12), 2263–2270 (2008).
   Google Scholar
• Hare KJ, Vilsboll T, Asmar M, Deacon CF, Knop FK, Holst JJ. The glucagonostatic and insulinotropic effects of glucagon-like peptide 1 contribute equally to its glucose-lowering action. Diabetes 59(7), 1765–1770 (2010).
   PubMed Web of Science ®Google Scholar
• Baggio LL, Drucker DJ. Biology of Incretins: GLP-1 and GIP. Gastroenterology 132(6), 2131–2157 (2007).
   PubMed Web of Science ®Google Scholar
• Astrup A, Rössner S, Van Gaal L et al. Effects of liraglutide in the treatment of obesity: a randomised, double-blind, placebo-controlled study. Lancet 374(9701), 1606–1616 (2007).
   Google Scholar
• Astrup A, Carraro R, Finer N et al. Safety, tolerability and sustained weight loss over 2 years with the once-daily human GLP-1 analog, liraglutide. Int. J. Obes. 36(6), 843–854 (2012).
   PubMed Web of Science ®Google Scholar
• Vrang N, Larsen PJ. Preproglucagon derived peptides GLP-1, GLP-2 and oxyntomodulin in the CNS: role of peripherally secreted and centrally produced peptides. Prog. Neurobiol. 92(3), 442–462 (2010).
   PubMed Web of Science ®Google Scholar
• Nauck MA. Incretin-based therapies for type 2 diabetes mellitus: properties, functions, and clinical implications. Am. J. Med. 124(1 Suppl.), S3–S18 (2011).
   PubMed Web of Science ®Google Scholar
• Davidson JA. Advances in therapy for type 2 diabetes: GLP-1 receptor agonists and DPP-4 inhibitors. Cleve. Clin. J. Med. 76( Suppl. 5), S28–S38 (2009).
   PubMedGoogle Scholar
• Dicker D. DPP-4 inhibitors: impact on glycemic control and cardiovascular risk factors. Diabetes Care 34( Suppl. 2), S276–S278 (2011).
   PubMed Web of Science ®Google Scholar
• Holst JJ. Glucagon and glucagon-like peptides 1 and 2. Results Probl. Cell Differ. 50, 121–135 (2010).
   PubMedGoogle Scholar
• Kissow H, Viby NE, Hartmann B et al. Exogenous glucagon-like peptide-2 (GLP-2) prevents chemotherapy-induced mucositis in rat small intestine. Cancer Chemother. Pharmacol. 70(1), 39–48 (2012).
   Google Scholar
• Askov-Hansen C, Jeppesen PB, Lund P, Hartmann B, Holst JJ, Henriksen DB. Effect of glucagon-like peptide-2 exposure on bone resorption: Effectiveness of high concentration versus prolonged exposure. Regul. Pept. 181, 4–8 (2013).
   Google Scholar
• Tang-Christensen M, Larsen PJ, Thulesen J, Romer J, Vrang N. The proglucagon-derived peptide, glucagon-like peptide-2, is a neurotransmitter involved in the regulation of food intake. Nat. Med. 6(7), 802–807 (2000).
   Google Scholar
• Sorensen LB, Flint A, Raben A, Hartmann B, Holst JJ, Astrup A. No effect of physiological concentrations of glucagon-like peptide-2 on appetite and energy intake in normal weight subjects. Int. J. Obes. Relat. Metab. Disord. 27(4), 450–456 (2003).
   PubMed Web of Science ®Google Scholar
• Schmidt PT, Näslund E, Grybäck P et al. Peripheral administration of GLP-2 to humans has no effect on gastric emptying or satiety. Regul. Pep. 116(1–3), 21–25 (2003).
   PubMed Web of Science ®Google Scholar
• Adrian TE, Ferri GL, Bacarese-Hamilton AJ, Fuessl HS, Polak JM, Bloom SR. Human distribution and release of a putative new gut hormone, peptide YY. Gastroenterology 89(5), 1070–1077 (1985).
   PubMed Web of Science ®Google Scholar
• Simpson K, Parker J, Plumer J, Bloom S. CCK, PYY and PP: the control of energy balance. Handb. Exp. Pharmacol. (209), 209–230 (2012).
   Google Scholar
• Lluis F, Fujimura M, Gomez G, Salva JA, Greeley GH Jr, Thompson JC. [Cellular localization, half-life, and secretion of peptide YY]. Rev. Esp. Fisiol. 45(4), 377–384 (1989).
   Google Scholar
• Rudnicki M, Kuvshinoff BW, McFadden DW. Extrinsic neural contribution to ileal peptide YY (PYY) release. J. Surg. Res. 52(6), 591–595 (1992).
   Google Scholar
• Batterham RL, Cowley MA, Small CJ et al. Physiology: does gut hormone PYY3-36 decrease food intake in rodents? (reply). Nature 430, 6996 (2004).
   Google Scholar
• Batterham RL, Cohen MA, Ellis SM et al. Inhibition of food intake in obese subjects by peptide YY3. N. Engl. J. Med. 349(10), 941–948 (2003).
   PubMed Web of Science ®Google Scholar
• De SA, Bloom SR. Gut hormones and appetite control: a focus on PYY and GLP-1 as therapeutic targets in obesity. Gut Liver 6(1), 10–20 (2012).
   Google Scholar
• Ghamari-Langroudi M, Colmers WF, Cone RD. PYY3-36 inhibits the action potential firing activity of POMC neurons of arcuate nucleus through postsynaptic Y2 receptors. Cell Metab. 2(3), 191–199 (2005).
   Google Scholar
• Holst JJ. Enteroglucagon. Ann. Rev. Physiol. 59, 257–271 (1997).
   PubMed Web of Science ®Google Scholar
• Read N, French S, Cunningham K. The role of the gut in regulating food intake in man. Nutr. Rev. 52(1), 1–10 (1994).
   Google Scholar
• Holst JJ. Evidence that enteroglucagon (II) is identical with the C-terminal sequence (residues 33–69) of glicentin. Biochem. J. 207(3), 381–388 (1982).
   PubMed Web of Science ®Google Scholar
• Bataille D, Gespach C, Tatemoto K et al. Bioactive enteroglucagon (oxyntomodulin): present knowledge on its chemical structure and its biological activities. Peptides 2( Suppl. 2), 41–44 (1981).
   PubMedGoogle Scholar
• Pocai A. Unraveling Oxyntomodulin, GLP-1’s enigmatic brother. J. Endocrinology 215(3), 335–346 (2012).
   PubMed Web of Science ®Google Scholar
• Wynne K, Bloom SR. The role of oxyntomodulin and peptide tyrosine-tyrosine (PYY) in appetite control. Nat. Clin. Pract. Endocrinol. Metab. 2(11), 612–620 (2006).
   Google Scholar
• Jarrousse C, Bataille D, Jeanrenaud B. A pure enteroglucagon, oxyntomodulin (glucagon 37), stimulates insulin release in perfused rat pancreas. Endocrinology 115(1), 102–105 (1984).
   Google Scholar
• Wynne K, Field BC, Bloom SR. The mechanism of action for oxyntomodulin in the regulation of obesity. Curr. Opin. Investig. Drugs 11(10), 1151–1157 (2010).
   PubMedGoogle Scholar
• Wynne K, Park AJ, Small CJ et al. Oxyntomodulin increases energy expenditure in addition to decreasing energy intake in overweight and obese humans: a randomised controlled trial. Int. J. Obes. (Lond.) 30(12), 1729–1736 (2006).
   PubMed Web of Science ®Google Scholar
• Dakin CL, Small CJ, Batterham RL et al. Peripheral oxyntomodulin reduces food intake and body weight gain in rats. Endocrinology 145(6), 2687–2695 (2004).
   PubMed Web of Science ®Google Scholar
• Dakin CL, Gunn I, Small CJ et al. Oxyntomodulin inhibits food intake in the rat. Endocrinology 142(10), 4244–4250 (2001).
   PubMed Web of Science ®Google Scholar
• Kosinski JR, Hubert J, Carrington PE et al. The glucagon receptor is involved in mediating the body weight-lowering effects of oxyntomodulin. Obes. (Silver Spring) 20(8), 1566–1571(2012).
   PubMed Web of Science ®Google Scholar
• Pocai A, Carrington PE, Adams JR et al. Glucagon-like peptide 1/glucagon receptor dual agonism reverses obesity in mice. Diabetes 58(10), 2258–2266 (2009).
   PubMed Web of Science ®Google Scholar
• Druce MR , Bloom SR. Oxyntomodulin: a novel potential treatment for obesity. Treat. Endocrinol. 5(5), 265–272 (2006).
   PubMedGoogle Scholar
• Lopez LC, Frazier ML, Su CJ, Kumar A, Saunders GF. Mammalian pancreatic preproglucagon contains three glucagon-related peptides. Proc. Natl Acad. Sci.USA 80(18), 5485–5489 (1983).
   Google Scholar
• Blache P, Kervran A, Bataille D. Oxyntomodulin and glicentin: brain-gut peptides in the rat. Endocrinology 123(6), 2782–2787 (1988).
   Google Scholar
• Tomita R, Igarashi S, Tanjoh K, Fujisaki S. Role of recombinant human glicentin in the normal human jejunum: an in vitro study. Hepatogastroenterology 52(65), 1459–1462 (2005).
   Google Scholar
• Mustain WC, Rychahou PG, Evers BM. The role of neurotensin in physiologic and pathologic processes. Curr. Opin. Endocrinol. Diabetes Obes. 18(1), 75–82 (2011).
   PubMedGoogle Scholar
• Jacobsen L, Madsen P, Jacobsen C, Nielsen MS, Gliemann J, Petersen CM. Activation and functional characterization of the mosaic receptor SorLA/LR11. J. Biol. Chem. 276(25), 22788–22796 (2001).
   PubMed Web of Science ®Google Scholar
• Christ-Crain M, Stoeckli R, Ernst A et al. Effect of gastric bypass and gastric banding on neurotensin levels in morbidly obese patients. J. Clin. Endocrinol. Metab. 91(9), 3544–3547 (2006).
   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. J. Clin. Invest. 22(4), 283–291 (1992).
   PubMed Web of Science ®Google Scholar
• de Bruine AP, Dinjens WN, Pijls MM et al. NCI-H716 cells as a model for endocrine differentiation in colorectal cancer. Virchows Arch. B Cell Pathol. Incl. Mol. Pathol. 62(5), 311–320 (1992).
   Google Scholar
• Drucker DJ, Jin T, Asa SL, Young TA, Brubaker PL. Activation of proglucagon gene transcription by protein kinase-A in a novel mouse enteroendocrine cell line. Mol. Endocrinol. 8(12), 1646–1655 (1994).
   PubMedGoogle Scholar
• Rindi G, Grant SG, Yiangou Y et al. Development of neuroendocrine tumors in the gastrointestinal tract of transgenic mice. Heterogeneity of hormone expression. Am. J. Pathol. 136(6), 1349–1363 (1990).
   Web of Science ®Google Scholar
• Reimann F, Habib AM, Tolhurst G, Parker HE, Rogers GJ, Gribble FM. glucose sensing in L cells: a primary cell study. Cell Metab. 8(6), 532–539 (2008).
   PubMed Web of Science ®Google Scholar
• Jacobsen SH, Olesen SC, Dirksen C et al. Changes in gastrointestinal hormone responses, insulin sensitivity, and beta-cell function within 2 weeks after gastric bypass in non-diabetic subjects. Obes. Surg. 22(7), 1084–1096 (2012).
   PubMed Web of Science ®Google Scholar
• Gorboulev V, Schürmann A, Vallon V et al. Na+-d-glucose cotransporter SGLT1 is pivotal for intestinal glucose absorption and glucose-dependent incretin secretion. Diabetes 61(1), 187–196 (2012).
   PubMed Web of Science ®Google Scholar
• Parker HE, Adriaenssens A, Rogers G et al. Predominant role of active versus facilitative glucose transport for glucagon-like peptide-1 secretion. Diabetologia 55(9), 2445–2455 (2012).
   PubMed Web of Science ®Google Scholar
• Diakogiannaki E, Gribble FM, Reimann F. Nutrient detection by incretin hormone secreting cells. Physiol. Behav. 106(3), 387–393 (2012).
   Google Scholar
• Yoder SM, Yang Q, Kindel TL, Tso P. Stimulation of incretin secretion by dietary lipid: is it dose dependent? Am. J. Physiol. Gastrointest. Liver Physiol. 297(2), G299–G305 (2009).
   Google Scholar
• Murphy MC, Isherwood SG, Sethi S et al. Postprandial lipid and hormone responses to meals of varying fat contents: modulatory role of lipoprotein lipase? Eur. J. Clin. Nutr. 49(8), 578–588 (1995).
   Google Scholar
• Engelstoft MS, Egerod KL, Holst B, Schwartz TW. A gut feeling for obesity: 7TM sensors on enteroendocrine cells. Cell Metab. 8(6), 447–449 (2008).
   Google Scholar
• Chu ZL, Carroll C, Alfonso J et al. A role for intestinal endocrine cell-expressed G protein-coupled receptor 119 in glycemic control by enhancing glucagon-like peptide-1 and glucose-dependent insulinotropic peptide release. Endocrinol. 149(5), 2038–2047 (2008).
   PubMed Web of Science ®Google Scholar
• Rodriguez de Fonseca F, Navarro M, Gomez R et al. An anorexic lipid mediator regulated by feeding. Nature 414(6860), 209–212 (2001).
   PubMed Web of Science ®Google Scholar
• Hansen KB, Rosenkilde MM, Knop FK et al. 2-Oleoyl glycerol is a GPR119 agonist and signals GLP−1 release in humans. J. Clin. Endocrinol. Metab. 96(9), E1409–E1417 (2011).
   PubMed Web of Science ®Google Scholar
• Overton HA, Babbs AJ, Doel SM et al. Deorphanization of a G protein-coupled receptor for oleoylethanolamide and its use in the discovery of small-molecule hypophagic agents. Cell Metab. 3(3), 167–175 (2006).
   PubMed Web of Science ®Google Scholar
• Parker HE, Wallis K, le Roux CW, Wong KY, Reimann F, Gribble FM. Molecular mechanisms underlying bile acid-stimulated glucagon-like peptide-1 secretion. Br. J. Pharmacol. 165(2), 414–423 (2012).
   PubMed Web of Science ®Google Scholar
• Hansen M, Sonne DP, Mikkelsen KH, Gluud LL, Vilsböll T, Knop FK. Effect of bile acid sequestrants on glycaemic control: protocol for a systematic review with meta-analysis of randomised controlled trials. BMJ Open 2(6) (2012).
   Google Scholar
• Reimer RA. Meat hydrolysate and essential amino acid-induced glucagon-like peptide-1 secretion, in the human NCI-H716 enteroendocrine cell line, is regulated by extracellular signal-regulated kinase1/2 and p38 mitogen-activated protein kinases. J. Endocrinol. 191(1), 159–170 (2006).
   Google Scholar
• Cordier-Bussat M, Bernard C, Levenez F et al. Peptones stimulate both the secretion of the incretin hormone glucagon-like peptide 1 and the transcription of the proglucagon gene. Diabetes 47(7), 1038–1045 (1998).
   Google Scholar
• Reimann F. Molecular mechanisms underlying nutrient detection by incretin-secreting cells. Int. Dairy J. 20(4), 236–242 (2010).
   Google Scholar
• Reimann F, Williams L, Silva Xavier G, Rutter GA, Gribble FM. Glutamine potently stimulates glucagon-like peptide-1 secretion from GLUTag cells. Diabetologia 47(9), 1592–1601 (2004).
   PubMed Web of Science ®Google Scholar
• Greenfield JR, Farooqi IS, Keogh JM et al. Oral glutamine increases circulating glucagon-like peptide 1, glucagon, and insulin concentrations in lean, obese, and type 2 diabetic subjects. Am. J. Clin. Nutr. 89(1), 106–113 (2009).
   PubMed Web of Science ®Google Scholar
• Zambrowicz B, Freiman J, Brown PM et al. LX4211, a dual SGLT1/SGLT2 inhibitor, improved glycemic control in patients with type 2 diabetes in a randomized, placebo-controlled trial. Clin. Pharmacol. Ther. 92(2), 158–169 (2012).
   PubMed Web of Science ®Google Scholar
• Zambrowicz B, Ding ZM, Ogbaa I et al. Effects of LX4211, a dual SGLT1/SGLT2 inhibitor, plus sitagliptin on postprandial active GLP-1 and glycemic control in type 2 diabetes. Clin. Ther. 35(3), 273–285 (2013).
   PubMed Web of Science ®Google Scholar
• Powell DR, Smith M, Greer J et al. LX4211 Increases serum glucagon-like peptide 1 and peptide YY levels by reducing sodium/glucose cotransporter 1 (SGLT1)-mediated absorption of intestinal glucose. J. Pharmacol. Exp. Ther. 345(2), 250–259 (2013).
   PubMed Web of Science ®Google Scholar
• Shibazaki T, Tomae M, Ishikawa-Takemura Y et al. KGA-2727, a novel selective inhibitor of a high-affinity sodium glucose cotransporter (SGLT1), exhibits antidiabetic efficacy in rodent models. J. Pharmacol. Exp. Ther. 342(2), 288–296 (2012).
   PubMed Web of Science ®Google Scholar
• Katz LB, Gambale JJ, Rothenberg PL et al. Pharmacokinetics, pharmacodynamics, safety, and tolerability of JNJ-38431055, a novel GPR119 receptor agonist and potential antidiabetes agent, in healthy male subjects. Clin. Pharmacol. Ther. 90(5), 685–692 (2011).
   Google Scholar
• Flock G, Holland D, Seino Y, Drucker DJ. GPR119 regulates murine glucose homeostasis through incretin receptor-dependent and independent mechanisms. Endocrinology 152(2), 374–383 (2011).
   Google Scholar
• Thomas C, Gioiello A, Noriega L et al. TGR5-mediated bile acid sensing controls glucose homeostasis. Cell Metab. 10(3), 167–177 (2009).
   PubMed Web of Science ®Google Scholar
• Shang Q, Saumoy M, Holst JJ, Salen G, Xu G. Colesevelam improves insulin resistance in a diet-induced obesity (F-DIO) rat model by increasing the release of GLP-1. Am. J. Physiol. Gastrointest. Liver Physiol. 298(3), G419–G424 (2010).
   PubMed Web of Science ®Google Scholar
• Adrian TE, Gariballa S, Parekh KA et al. Rectal taurocholate increases L cell and insulin secretion, and decreases blood glucose and food intake in obese type 2 diabetic volunteers. Diabetologia 55(9), 2343–2347 (2012).
   PubMed Web of Science ®Google Scholar
• Xiong Y, Swaminath G, Cao Q et al. Activation of FFA1 mediates GLP-1 secretion in mice. Evidence for allosterism at FFA1. Mol. Cell. Endocrinol. 369(1–2), 119–129 (2013).
   Google Scholar
• Luo J, Swaminath G, Brown SP et al. A Potent class of GPR40 full agonists engages the enteroinsular axis to promote glucose control in rodents. PLoS ONE 7(10), e46300 (2012).
   PubMed Web of Science ®Google Scholar
• Ahlkvist L, Vikman J, Pacini G, Ahren B. Synergism by individual macronutrients explains the marked early GLP-1 and islet hormone responses to mixed meal challenge in mice. Regul. Pep. 178(1–3), 29–35 (2012).
   Google Scholar
• Migoya EM, Bergeron R, Miller JL et al. Dipeptidyl peptidase-4 inhibitors administered in combination with metformin result in an additive increase in the plasma concentration of active GLP-1. Clin. Pharmacol. Ther. 88(6), 801–808 (2010).
   PubMed Web of Science ®Google Scholar