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Molecular mechanisms underlying nutrient-stimulated incretin secretion

Published online by Cambridge University Press:  05 January 2010

Helen E. Parker ,
Frank Reimann  and
Fiona M. Gribble
Helen E. Parker
Affiliation:
Cambridge Institute for Medical Research and Department of Clinical Biochemistry, Addenbrooke's Hospital, Cambridge, CB2 0XY, UK.
Frank Reimann
Affiliation:
Cambridge Institute for Medical Research and Department of Clinical Biochemistry, Addenbrooke's Hospital, Cambridge, CB2 0XY, UK.
Fiona M. Gribble*
Affiliation:
Cambridge Institute for Medical Research and Department of Clinical Biochemistry, Addenbrooke's Hospital, Cambridge, CB2 0XY, UK.
*
*Corresponding author: Fiona M. Gribble, Cambridge Institute for Medical Research, Wellcome Trust/MRC Building, Addenbrooke's Hospital, Hills Road, Cambridge, CB2 0XY, UK. E-mail: fmg23@cam.ac.uk
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Abstract

The incretin hormones glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are released from enteroendocrine cells in the intestinal epithelium in response to nutrient ingestion. The actions of GLP-1 and GIP – not only on local gut physiology but also on glucose homeostasis, appetite control and fat metabolism – have made these hormones an attractive area for drug discovery programmes. The potential range of strategies to target the secretion of these hormones therapeutically has been limited by an incomplete understanding of the mechanisms underlying their release. The use of organ and whole-animal perfusion techniques, cell line models and primary L- and K-cells has led to the identification of a variety of pathways involved in the sensing of carbohydrate, fat and protein in the gut lumen. This review focuses on our current understanding of these signalling mechanisms that might underlie nutrient responsiveness of L- and K-cells.

Type
Review Article
Information
Expert Reviews in Molecular Medicine , Volume 12 , January 2010 , e1
Copyright
Copyright © Cambridge University Press 2010

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References

References

1Creutzfeldt, W. (2005) The [pre-] history of the incretin concept. Regulatory Peptides 128, 87-91CrossRefGoogle ScholarPubMed
2Moore, B., Edie, E.S. and Abram, J.H. (1906) On the treatment of diabetes mellitus by acid extract of duodenal mucous membrane. Biochemical Journal 1, 28-38CrossRefGoogle Scholar
3Rehfeld, J.F. (2004) A centenary of gastrointestinal endocrinology. Hormone and Metabolic Research 36, 735-741CrossRefGoogle ScholarPubMed
4Elrick, H. et al. (1964) Plasma insulin response to oral and intravenous glucose administration. Journal of Clinical Endocrinology and Metabolism 24, 1076-1082CrossRefGoogle ScholarPubMed
5Creutzfeldt, W. (1979) The incretin concept today. Diabetologia 16, 75-85CrossRefGoogle ScholarPubMed
6Baggio, L. and Drucker, D. (2007) Biology of incretins: GLP-1 and GIP. Gastroenterology 132, 2131-2157CrossRefGoogle ScholarPubMed
7Holst, J.J. (2007) The physiology of glucagon-like peptide 1. Physiological Reviews 87, 1409-1439CrossRefGoogle ScholarPubMed
8Gromada, J., Holst, J.J. and Rorsman, P. (1998) Cellular regulation of islet hormone secretion by the incretin hormone glucagon-like peptide 1. Pflugers Archiv (European Journal of Physiology) 435, 583-594Google Scholar
9Eissele, R. et al. (1992) Glucagon-like peptide-1 cells in the gastrointestinal tract and pancreas of rat, pig and man. European Journal of Clinical Investigation 22, 283-291CrossRefGoogle Scholar
10Polak, J.M. et al. (1973) Cellular localization of gastric inhibitory polypeptide in the duodenum and jejunum. Gut 14, 284-288CrossRefGoogle ScholarPubMed
11Buchan, A.M. et al. (1978) Electronimmunocytochemical evidence for the K cell localization of gastric inhibitory polypeptide (GIP) in man. Histochemistry 56, 37-44CrossRefGoogle Scholar
12Herrmann, C. et al. (1995) Glucagon-like peptide-1 and glucose-dependent insulin-releasing polypeptide plasma levels in response to nutrients. Digestion 56, 117-126CrossRefGoogle ScholarPubMed
13Cataland, S. et al. (1974) Gastric inhibitory polypeptide (GIP) stimulation by oral glucose in man. Journal of Clinical Endocrinology and Metabolism 39, 223-228CrossRefGoogle ScholarPubMed
14Elliott, R.M. et al. (1993) Glucagon-like peptide-1 (7-36)amide and glucose-dependent insulinotropic polypeptide secretion in response to nutrient ingestion in man: acute post-prandial and 24-h secretion patterns. Journal of Endocrinology 138, 159-166CrossRefGoogle ScholarPubMed
15Balks, H.J. et al. (1997) Rapid oscillations in plasma glucagon-like peptide-1 (GLP-1) in humans: cholinergic control of GLP-1 secretion via muscarinic receptors. Journal of Clinical Endocrinology and Metabolism 82, 786-790Google ScholarPubMed
16Schirra, J. et al. (1996) Gastric emptying and release of incretin hormones after glucose ingestion in humans. Journal of Clinical Investigation 97, 92-103CrossRefGoogle ScholarPubMed
17Hansen, L. and Holst, J.J. (2002) The effects of duodenal peptides on glucagon-like peptide-1 secretion from the ileum. A duodeno–ileal loop? Regulatory Peptides 110, 39-45CrossRefGoogle ScholarPubMed
18Rocca, A.S. and Brubaker, P.L. (1999) Role of the vagus nerve in mediating proximal nutrient-induced glucagon-like peptide-1 secretion. Endocrinology 140, 1687-1694CrossRefGoogle ScholarPubMed
19Mortensen, K. et al. (2003) GLP-1 and GIP are colocalized in a subset of endocrine cells in the small intestine. Regulatory Peptides 114, 189-196CrossRefGoogle Scholar
20Theodorakis, M.J. et al. (2006) Human duodenal enteroendocrine cells: source of both incretin peptides, GLP-1 and GIP. American Journal of Physiology, Endocrinology and Metabolism 290, 550-559CrossRefGoogle ScholarPubMed
21Nauck, M.A. et al. (1996) Release of glucagon-like peptide 1 (GLP-1 [7-36 amide]), gastric inhibitory polypeptide (GIP) and insulin in response to oral glucose after upper and lower intestinal resections. Zeitschrift fuer Gastroenterologie 34, 159-166Google Scholar
22Orskov, C., Wettergren, A. and Holst, J.J. (1993) Biological effects and metabolic rates of glucagonlike peptide-1 7-36 amide and glucagonlike peptide-1 7-37 in healthy subjects are indistinguishable. Diabetes 42, 658-661CrossRefGoogle ScholarPubMed
23Meier, J.J. and Nauck, M.A. (2005) Glucagon-like peptide 1(GLP-1) in biology and pathology. Diabetes/Metabolism Research and Reviews 21, 91-117CrossRefGoogle Scholar
24Baggio, L.L. et al. (2004) Oxyntomodulin and glucagon-like peptide-1 differentially regulate murine food intake and energy expenditure. Gastroenterology 127, 546-558CrossRefGoogle ScholarPubMed
25Druce, M.R. et al. (2009) Investigation of structure-activity relationships of oxyntomodulin (Oxm) using Oxm analogs. Endocrinology 150, 1712-1722CrossRefGoogle ScholarPubMed
26Ugleholdt, R. et al. (2006) Prohormone convertase 1/3 is essential for processing of the glucose-dependent insulinotropic polypeptide precursor. Journal of Biological Chemistry 281, 11050-11057CrossRefGoogle ScholarPubMed
27Demuth, H., McIntosh, C. and Pederson, R. (2005) Type 2 diabetes–therapy with dipeptidyl peptidase IV inhibitors. Biochimica et Biophysica Acta 1751, 33-44Google Scholar
28Hansen, L. et al. (1999) 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, 5356-5363CrossRefGoogle Scholar
29Mentlein, R. (1999) Dipeptidyl-peptidase IV (CD26)–role in the inactivation of regulatory peptides. Regulatory Peptides 85, 9-24Google Scholar
30Deacon, C.F. et al. (2000) 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. Journal of Clinical Endocrinology and Metabolism 85, 3575-3581Google ScholarPubMed
31Kieffer, T.J., McIntosh, C.H. and Pederson, R.A. (1995) Degradation of glucose-dependent insulinotropic polypeptide and truncated glucagon-like peptide 1 in vitro and in vivo by dipeptidyl peptidase IV. Endocrinology 136, 3585-3596CrossRefGoogle ScholarPubMed
32Vahl, T.P. et al. (2007) 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, 4965-4973Google Scholar
33Bucinskaite, V. et al. (2009) Receptor-mediated activation of gastric vagal afferents by glucagon-like peptide-1 in the rat. Neurogastroenterology and Motility 21, 978-e78CrossRefGoogle ScholarPubMed
34Nakagawa, A. et al. (2004) Receptor gene expression of glucagon-like peptide-1, but not glucose-dependent insulinotropic polypeptide, in rat nodose ganglion cells. Autonomic Neuroscience 110, 36-43CrossRefGoogle Scholar
35Kakei, M. et al. (2002) Glucagon-like peptide-1 evokes action potentials and increases cytosolic Ca2+ in rat nodose ganglion neurons. Autonomic Neuroscience 102, 39-44CrossRefGoogle ScholarPubMed
36Simasko, S.M. and Ritter, R.C. (2003) Cholecystokinin activates both A- and C-type vagal afferent neurons. American Journal of Physiology – Gastrointestinal and Liver Physiology 285, G1204-1213CrossRefGoogle ScholarPubMed
37Simasko, S.M. et al. (2002) Cholecystokinin increases cytosolic calcium in a subpopulation of cultured vagal afferent neurons. American Journal of Physiology – Regulatory Integrative and Comparative Physiology 283, R1303-1313Google Scholar
38Williams, D.L., Baskin, D.G. and Schwartz, M.W. (2009) Evidence that intestinal glucagon-like peptide-1 plays a physiological role in satiety. Endocrinology 150, 1680-1687CrossRefGoogle Scholar
39Drucker, D. et al. (1994) Activation of proglucagon gene transcription by protein kinase-A in a novel mouse enteroendocrine cell line. Molecular Endocrinology 8, 1646-1655Google Scholar
40Brubaker, P.L., Schloos, J. and Drucker, D.J. (1998) Regulation of glucagon-like peptide-1 synthesis and secretion in the GLUTag enteroendocrine cell line. Endocrinology 139, 4108-4114CrossRefGoogle ScholarPubMed
41Rindi, G. et al. (1990) Development of neuroendocrine tumors in the gastrointestinal tract of transgenic mice. Heterogeneity of hormone expression. American Journal of Pathology 136, 1349-1363Google ScholarPubMed
42Ramshur, E.B., Rull, T.R. and Wice, B.M. (2002) Novel insulin/GIP co-producing cell lines provide unexpected insights into Gut K-cell function in vivo. Journal of Cellular Physiology 192, 339-350CrossRefGoogle ScholarPubMed
43Cheung, A.T. et al. (2000) Glucose-dependent insulin release from genetically engineered K cells. Science 290, 1959-1962CrossRefGoogle ScholarPubMed
44Kieffer, T.J. et al. (1995) Gastric inhibitory polypeptide release from a tumor-derived cell line. American Journal of Physiology 269, E316-322Google ScholarPubMed
45Reimer, R.A. et al. (2001) A human cellular model for studying the regulation of glucagon-like peptide-1 secretion. Endocrinology 142, 4522-4528Google Scholar
46Cao, X. et al. (2003) Aberrant regulation of human intestinal proglucagon gene expression in the NCI-H716 cell line. Endocrinology 144, 2025-2033CrossRefGoogle ScholarPubMed
47Brubaker, P.L. and Vranic, M. (1987) Fetal rat intestinal cells in monolayer culture: a new in vitro system to study the glucagon-like immunoreactive peptides. Endocrinology 120, 1976-1985Google Scholar
48Kieffer, T.J. et al. (1994) Release of gastric inhibitory polypeptide from cultured canine endocrine cells. American Journal of Physiology 267, E489-496Google ScholarPubMed
49Damholt, A.B., Buchan, A.M. and Kofod, H. (1998) Glucagon-like-peptide-1 secretion from canine L-cells is increased by glucose-dependent-insulinotropic peptide but unaffected by glucose. Endocrinology 139, 2085-2091CrossRefGoogle ScholarPubMed
50Reimann, F. et al. (2008) Glucose sensing in L cells: a primary cell study. Cell Metabolism 8, 532-539CrossRefGoogle Scholar
51Parker, H.E. et al. (2009) Nutrient-dependent secretion of glucose-dependent insulinotropic polypeptide from primary murine K cells. Diabetologia 52, 289-298CrossRefGoogle ScholarPubMed
52Reimann, F. and Gribble, F.M. (2002) Glucose-sensing in glucagon-like peptide-1-secreting cells. Diabetes 51, 2757-2763CrossRefGoogle ScholarPubMed
53Nielsen, L.B. et al. (2007) Co-localisation of the Kir6.2/SUR1 channel complex with glucagon-like peptide-1 and glucose-dependent insulinotrophic polypeptide expression in human ileal cells and implications for glycaemic control in new onset type 1 diabetes. European Journal of Endocrinology 156, 663-671CrossRefGoogle ScholarPubMed
54Matschinsky, F. (2002) Regulation of pancreatic beta-cell glucokinase: from basics to therapeutics. Diabetes 51, 394-404CrossRefGoogle ScholarPubMed
55Glaser, B. et al. (1998) Familial hyperinsulinism caused by an activating glucokinase mutation. New England Journal of Medicine 338, 226-230CrossRefGoogle ScholarPubMed
56Stoffel, M. et al. (1992) Missense glucokinase mutation in maturity-onset diabetes of the young and mutation screening in late-onset diabetes. Nature Genetics 2, 153-156CrossRefGoogle ScholarPubMed
57Jetton, T.L. et al. (1994) Analysis of upstream glucokinase promoter activity in transgenic mice and identification of glucokinase in rare neuroendocrine cells in the brain and gut. Journal of Biological Chemistry 269, 3641-3654CrossRefGoogle ScholarPubMed
58El-Ouaghlidi, A. et al. (2007) The dipeptidyl peptidase 4 inhibitor vildagliptin does not accentuate glibenclamide-induced hypoglycemia but reduces glucose-induced glucagon-like peptide 1 and gastric inhibitory polypeptide secretion. Journal of Clinical Endocrinology and Metabolism 92, 4165-4171CrossRefGoogle Scholar
59Murphy, R. et al. (2009) Glucokinase, the pancreatic glucose sensor, is not the gut glucose sensor. Diabetologia 52, 154-159CrossRefGoogle Scholar
60Miki, T. et al. (2005) Distinct effects of glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 on insulin secretion and gut motility. Diabetes 54, 1056-1063Google Scholar
61Vollmer, K. et al. (2009) Hyperglycemia acutely lowers the postprandial excursions of glucagon-like Peptide-1 and gastric inhibitory polypeptide in humans. Journal of Clinical Endocrinology and Metabolism 94, 1379-1385CrossRefGoogle ScholarPubMed
62Hansen, L. et al. (2004) Glucagon-like peptide-1 secretion is influenced by perfusate glucose concentration and by a feedback mechanism involving somatostatin in isolated perfused porcine ileum. Regulatory Peptides 118, 11-18CrossRefGoogle ScholarPubMed
63Sykes, S. et al. (1980) Evidence for preferential stimulation of gastric inhibitory polypeptide secretion in the rat by actively transported carbohydrates and their analogues. Journal of Endocrinology 85, 201-207CrossRefGoogle ScholarPubMed
64Gribble, F.M. et al. (2003) A novel glucose-sensing mechanism contributing to glucagon-like peptide-1 secretion from the GLUTag cell line. Diabetes 52, 1147-1154CrossRefGoogle ScholarPubMed
65Ritzel, U. et al. (1997) Release of glucagon-like peptide-1 (GLP-1) by carbohydrates in the perfused rat ileum. Acta Diabetologica 34, 18-21CrossRefGoogle ScholarPubMed
66Wright, E.M. and Turk, E. (2004) The sodium/glucose cotransport family SLC5. Pflugers Archiv (European Journal of Physiology) 447, 510-518Google ScholarPubMed
67Gonzalez, J.A., Reimann, F. and Burdakov, D. (2009) Dissociation between sensing and metabolism of glucose in sugar sensing neurones. Journal of Physiology 587, 41-48CrossRefGoogle ScholarPubMed
68Diez-Sampedro, A. et al. (2000) Glycoside binding and translocation in Na+-dependent glucose cotransporters: comparison of SGLT1 and SGLT3. Journal of Membrane Biology 176, 111-117CrossRefGoogle ScholarPubMed
69Jang, H.J. et al. (2007) Gut-expressed gustducin and taste receptors regulate secretion of glucagon-like peptide-1. Proceedings of the National Academy of Sciences of the United States of America 104, 15069-15074CrossRefGoogle ScholarPubMed
70Rozengurt, E. and Sternini, C. (2007) Taste receptor signaling in the mammalian gut. Current Opinion in Pharmacology 7, 557-562CrossRefGoogle ScholarPubMed
71Dyer, J. et al. (2005) Expression of sweet taste receptors of the T1R family in the intestinal tract and enteroendocrine cells. Biochemical Society Transactions 33, 302-305CrossRefGoogle ScholarPubMed
72Wu, S.V. et al. (2002) Expression of bitter taste receptors of the T2R family in the gastrointestinal tract and enteroendocrine STC-1 cells. Proceedings of the National Academy of Sciences of the United States of America 99, 2392-2397CrossRefGoogle ScholarPubMed
73Rozengurt, N. et al. (2006) Colocalization of the alpha-subunit of gustducin with PYY and GLP-1 in L cells of human colon. Amerian Journal of Physiology – Gastrointestinal and Liver Physiology 291, G792-802CrossRefGoogle Scholar
74Fujita, Y. et al. (2009) Incretin release from gut is acutely enhanced by sugar but not by sweeteners in vivo. American Journal of Physiology – Endocrinology and Metabolism 296, E473-479CrossRefGoogle Scholar
75Little, T.J. et al. (2009) Sweetness and bitterness taste of meals per se does not mediate gastric emptying in humans. American Journal of Physiology – Regulatory Integrative and Comparative Physiology 297, R632-639CrossRefGoogle Scholar
76Ma, J. et al. (2009) Effect of the artificial sweetener, sucralose, on gastric emptying and incretin hormone release in healthy subjects. American Journal of Physiology – Gastrointestinal and Liver Physiology 296, G735-739CrossRefGoogle ScholarPubMed
77Bezencon, C., le Coutre, J. and Damak, S. (2007) Taste-signaling proteins are coexpressed in solitary intestinal epithelial cells. Chemical Senses 32, 41-49CrossRefGoogle ScholarPubMed
78Chen, M.C. et al. (2006) Bitter stimuli induce Ca2+ signaling and CCK release in enteroendocrine STC-1 cells: role of L-type voltage-sensitive Ca2+ channels. American Journal of Physiology – Cell Physiology 291, C726-739CrossRefGoogle ScholarPubMed
79Dotson, C.D. et al. (2008) Bitter taste receptors influence glucose homeostasis. PLoS ONE 3, e3974CrossRefGoogle ScholarPubMed
80Kang, J. et al. (2001) Interactions of a series of fluoroquinolone antibacterial drugs with the human cardiac K+ channel HERG. Molecular Pharmacology 59, 122-126CrossRefGoogle ScholarPubMed
81Saraya, A. et al. (2004) Effects of fluoroquinolones on insulin secretion and beta-cell ATP-sensitive K+ channels. European Journal of Pharmacology 497, 111-117Google Scholar
82Nemoz-Gaillard, E. et al. (1998) Regulation of cholecystokinin secretion by peptones and peptidomimetic antibiotics in STC-1 cells. Endocrinology 139, 932-938CrossRefGoogle ScholarPubMed
83Cordier-Bussat, M. et al. (1998) Peptones stimulate both the secretion of the incretin hormone glucagon-like peptide 1 and the transcription of the proglucagon gene. Diabetes 47, 1038-1045CrossRefGoogle ScholarPubMed
84Reimer, R.A. (2006) 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. Journal of Endocrinology 191, 159-170CrossRefGoogle ScholarPubMed
85Matsumura, K. et al. (2005) Possible role of PEPT1 in gastrointestinal hormone secretion. Biochemical and Biophysical Research Communications 336, 1028-1032CrossRefGoogle ScholarPubMed
86Gameiro, A. et al. (2005) The neurotransmitters glycine and GABA stimulate glucagon-like peptide-1 release from the GLUTag cell line. Journal of Physiology 569, 761-772CrossRefGoogle ScholarPubMed
87Reimann, F. et al. (2004) Glutamine potently stimulates glucagon-like peptide-1 secretion from GLUTag cells. Diabetologia 47, 1592-1601CrossRefGoogle ScholarPubMed
88Greenfield, J.R. et al. (2009) Oral glutamine increases circulating glucagon-like peptide 1, glucagon, and insulin concentrations in lean, obese, and type 2 diabetic subjects. American Journal of Clinical Nutrition 89, 106-113CrossRefGoogle ScholarPubMed
89Dumoulin, V. et al. (1998) Peptide YY, glucagon-like peptide-1, and neurotensin responses to luminal factors in the isolated vascularly perfused rat ileum. Endocrinology 139, 3780-3786Google Scholar
90Pilichiewicz, A. et al. (2003) Effect of lipase inhibition on gastric emptying of, and the glycemic and incretin responses to, an oil/aqueous drink in type 2 diabetes mellitus. Journal of Clinical Endocrinology and Metabolism 88, 3829-3834CrossRefGoogle Scholar
91Enc, F.Y. et al. (2009) Orlistat accelerates gastric emptying and attenuates GIP release in healthy subjects. American Journal of Physiology – Gastrointestinal and Liver Physiology 296, G482-489CrossRefGoogle ScholarPubMed
92Ellrichmann, M. et al. (2008) Orlistat inhibition of intestinal lipase acutely increases appetite and attenuates postprandial glucagon-like peptide-1-(7-36)-amide-1, cholecystokinin, and peptide YY concentrations. Journal of Clinical Endocrinology and Metabolism 93, 3995-3998CrossRefGoogle ScholarPubMed
93Iakoubov, R. et al. (2007) Protein kinase Czeta is required for oleic acid-induced secretion of glucagon-like peptide-1 by intestinal endocrine L cells. Endocrinology 148, 1089-1098CrossRefGoogle ScholarPubMed
94Simpson, A. et al. (2007) Cyclic AMP triggers glucagon-like peptide-1 secretion from the GLUTag enteroendocrine cell line. Diabetologia 50, 2181-2189Google Scholar
95Brubaker, P.L. (1988) Control of glucagon-like immunoreactive peptide secretion from fetal rat intestinal cultures. Endocrinology 123, 220-226CrossRefGoogle ScholarPubMed
96Buchan, A.M. et al. (1987) Morphologic and physiologic studies of canine ileal enteroglucagon-containing cells in short-term culture. Gastroenterology 93, 791-800CrossRefGoogle ScholarPubMed
97Brubaker, P.L., Schloos, J. and Drucker, D.J. (1998) Regulation of glucagon-like peptide-1 synthesis and secretion in the GLUTag enteroendocrine cell line. Endocrinology 139, 4108-4114CrossRefGoogle ScholarPubMed
98Roberge, J.N. and Brubaker, P.L. (1993) Regulation of intestinal proglucagon-derived peptide secretion by glucose-dependent insulinotropic peptide in a novel enteroendocrine loop. Endocrinology 133, 233-240Google Scholar
99Overton, H.A. et al. (2006) Deorphanization of a G protein-coupled receptor for oleoylethanolamide and its use in the discovery of small-molecule hypophagic agents. Cell Metabolism 3, 167-175CrossRefGoogle Scholar
100Lan, H. et al. (2009) GPR119 is required for physiological regulation of glucagon-like peptide-1 secretion but not for metabolic homeostasis. Journal of Endocrinology 201, 219-230CrossRefGoogle Scholar
101Chu, Z.L. et al. (2008) 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. Endocrinology 149, 2038-2047CrossRefGoogle ScholarPubMed
102Kawamata, Y. et al. (2003) A G protein-coupled receptor responsive to bile acids. Journal of Biological Chemistry 278, 9435-9440CrossRefGoogle Scholar
103le Roux, C.W. et al. (2007) Gut hormones as mediators of appetite and weight loss after Roux-en-Y gastric bypass. Annals of Surgery 246, 780-785CrossRefGoogle ScholarPubMed
104Patti, M.E. et al. (2009) Serum bile acids are higher in humans with prior gastric bypass: potential contribution to improved glucose and lipid metabolism. Obesity (Silver Spring) 17, 1671-1677Google Scholar
105Plaisancie, P. et al. (1995) Luminal glucagon-like peptide-1(7-36) amide-releasing factors in the isolated vascularly perfused rat colon. Journal of Endocrinology 145, 521-526CrossRefGoogle ScholarPubMed
106Katsuma, S., Hirasawa, A. and Tsujimoto, G. (2005) Bile acids promote glucagon-like peptide-1 secretion through TGR5 in a murine enteroendocrine cell line STC-1. Biochemical and Biophysical Research Communications 329, 386-390CrossRefGoogle Scholar
107Abello, J. et al. (1994) Stimulation of glucagon-like peptide-1 secretion by muscarinic agonist in a murine intestinal endocrine cell line. Endocrinology 134, 2011-2017CrossRefGoogle Scholar
108Roberge, J.N., Gronau, K.A. and Brubaker, P.L. (1996) Gastrin-releasing peptide is a novel mediator of proximal nutrient-induced proglucagon-derived peptide secretion from the distal gut. Endocrinology 137, 2383-2388CrossRefGoogle ScholarPubMed
109Anini, Y., Hansotia, T. and Brubaker, P.L. (2002) Muscarinic receptors control postprandial release of glucagon-like peptide-1: in vivo and in vitro studies in rats. Endocrinology 143, 2420-2426CrossRefGoogle ScholarPubMed
110Reimann, F., Ward, P.S. and Gribble, F.M. (2006) Signalling mechanisms underlying the release of glucagon-like peptide-1. Diabetes 55, S78-S85CrossRefGoogle Scholar
111Tanaka, T. et al. (2008) Free fatty acids induce cholecystokinin secretion through GPR120. Naunyn-Schmiedeberg's Archives of Pharmacology 377, 523-527CrossRefGoogle ScholarPubMed
112Hirasawa, A. et al. (2005) Free fatty acids regulate gut incretin glucagon-like peptide-1 secretion through GPR120. Nature Medicine 11, 90-94CrossRefGoogle ScholarPubMed
113Edfalk, S., Steneberg, P. and Edlund, H. (2008) Gpr40 is expressed in enteroendocrine cells and mediates free fatty acid stimulation of incretin secretion. Diabetes 57, 2280-2287CrossRefGoogle ScholarPubMed
114Tanaka, T. et al. (2008) Cloning and characterization of the rat free fatty acid receptor GPR120: in vivo effect of the natural ligand on GLP-1 secretion and proliferation of pancreatic beta cells. Naunyn-Schmiedeberg's Archives of Pharmacology 377, 515-522CrossRefGoogle ScholarPubMed
115Wang, J. et al. (2006) Medium-chain fatty acids as ligands for orphan G protein-coupled receptor GPR84. Journal of Biological Chemistry 281, 34457-34464Google Scholar
116Tazoe, H. et al. (2008) Roles of short-chain fatty acids receptors, GPR41 and GPR43 on colonic functions. Journal of Physiology and Pharmacology 59 (Suppl 2), 251-262Google ScholarPubMed
117Karaki, S. et al. (2006) Short-chain fatty acid receptor, GPR43, is expressed by enteroendocrine cells and mucosal mast cells in rat intestine. Cell and Tissue Research 324, 353-360CrossRefGoogle ScholarPubMed
118Plaisancie, P. et al. (1995) Luminal glucagon-like peptide-1(7-36) amide-releasing factors in the isolated vascularly perfused rat colon. Journal of Endocrinology 145, 521-526CrossRefGoogle ScholarPubMed
119Longo, W.E. et al. (1991) Short-chain fatty acid release of peptide YY in the isolated rabbit distal colon. Scandinavian Journal of Gastroenterology 26, 442-448CrossRefGoogle ScholarPubMed
120Covington, D.K. et al. (2006) The G-protein-coupled receptor 40 family (GPR40-GPR43) and its role in nutrient sensing. Biochemical Society Transactions 34, 770-773CrossRefGoogle ScholarPubMed
121Hansen, L. et al. (2000) Somatostatin restrains the secretion of glucagon-like peptide-1 and -2 from isolated perfused porcine ileum. American Journal of Physiology – Endocrinology and Metabolism 278, E1010-1018CrossRefGoogle ScholarPubMed
122Nauck, M.A. et al. (1993) Normalization of fasting hyperglycaemia by exogenous glucagon-like peptide 1 (7-36 amide) in type 2 (non-insulin-dependent) diabetic patients. Diabetologia 36, 741-744CrossRefGoogle ScholarPubMed
123Drucker, D.J. and Nauck, M.A. (2006) The incretin system: glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in type 2 diabetes. The Lancet 368, 1696-1705CrossRefGoogle ScholarPubMed
124Grant, S.F. et al. (2006) Variant of transcription factor 7-like 2 (TCF7L2) gene confers risk of type 2 diabetes. Nature Genetics 38, 320-323CrossRefGoogle ScholarPubMed
125Schafer, S.A. et al. (2007) Impaired glucagon-like peptide-1-induced insulin secretion in carriers of transcription factor 7-like 2 (TCF7L2) gene polymorphisms. Diabetologia 50, 2443-2450Google Scholar
126Unoki, H. et al. (2008) SNPs in KCNQ1 are associated with susceptibility to type 2 diabetes in East Asian and European populations. Nature Genetics 40, 1098-1102CrossRefGoogle ScholarPubMed
127Mussig, K. et al. (2009) Association of type 2 diabetes candidate polymorphisms in KCNQ1 with incretin and insulin secretion. Diabetes 58, 1715-1720CrossRefGoogle ScholarPubMed
128Yip, G. and Wolfe, M. (1999) GIP biology and fat metabolism. Life Sciences 66, 91-103CrossRefGoogle Scholar
129Yip, R.G. et al. (1998) Functional GIP receptors are present on adipocytes. Endocrinology 139, 4004-4007CrossRefGoogle ScholarPubMed
130Eckel, R.H., Fujimoto, W.Y. and Brunzell, J.D. (1979) Gastric inhibitory polypeptide enhanced lipoprotein lipase activity in cultured preadipocytes. Diabetes 28, 1141-1142CrossRefGoogle ScholarPubMed
131Kim, S.J., Nian, C. and McIntosh, C.H. (2007) Activation of lipoprotein lipase by glucose-dependent insulinotropic polypeptide in adipocytes. A role for a protein kinase B, LKB1, and AMP-activated protein kinase cascade. Journal of Biological Chemistry 282, 8557-8567Google ScholarPubMed
132Althage, M.C. et al. (2008) Targeted ablation of glucose-dependent insulinotropic polypeptide-producing cells in transgenic mice reduces obesity and insulin resistance induced by a high fat diet. Journal of Biological Chemistry 283, 18365-18376CrossRefGoogle ScholarPubMed
133McClean, P.L. et al. (2007) GIP receptor antagonism reverses obesity, insulin resistance, and associated metabolic disturbances induced in mice by prolonged consumption of high-fat diet. American Journal of Physiology – Endocrinology and Metabolism 293, E1746-1755CrossRefGoogle ScholarPubMed
134Nauck, M. et al. (1993) 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. Journal of Clinical Investigation 91, 301-307CrossRefGoogle Scholar
135Rouillé, Y., Martin, S. and Steiner, D.F. (1995) Differential processing of proglucagon by the subtilisin-like prohormone convertases PC2 and PC3 to generate either glucagon or glucagon-like peptide. Journal of Biological Chemistry 270, 26488–16496CrossRefGoogle ScholarPubMed

Further reading, resources and contacts

Holst, J.J. (2007) The physiology of glucagon-like peptide 1. Physiological Reviews 87, 1409-1439Google Scholar
http://www.glucagon.com/Google Scholar