On the role of the incretin hormones GIP and GLP-1 in the pathogenesis of type 2 diabetes mellitus

Danish Medical Bulletin

Volumn 51, Issue 4, 2004, Pages 364-370

  Vilsbøll, Tina ^a,b,c,d  

^a GENTOFTE UNIVERSITY HOSPITAL   (Denmark)

^b UNIVERSITY OF COPENHAGEN   (Denmark)

^c HVIDOVRE HOSPITAL   (Denmark)

^d NONE   (Denmark)

Author keywords

[No Author keywords available]

Indexed keywords

DIPEPTIDYL PEPTIDASE IV; GASTRIC INHIBITORY POLYPEPTIDE; GLUCAGON LIKE PEPTIDE 1;

CONCENTRATION (PARAMETERS); GENE EXPRESSION; GENE SEQUENCE; GENETIC VARIABILITY; HORMONE BLOOD LEVEL; HORMONE METABOLISM; HORMONE RELEASE; HUMAN; INSULIN RELEASE; MOLECULAR MECHANICS; NON INSULIN DEPENDENT DIABETES MELLITUS; PANCREAS ISLET BETA CELL; PATHOGENESIS; PROTEIN FUNCTION; REVIEW; SEQUENCE HOMOLOGY;

DIABETES MELLITUS, TYPE 2; GASTRIC INHIBITORY POLYPEPTIDE; GLUCAGON-LIKE PEPTIDE 1; GLUCAGON-LIKE PEPTIDE 2; GLUCAGON-LIKE PEPTIDES; HUMANS; INSULIN;

EID: 27244447025     PISSN: 16039629     EISSN: 16039629     Source Type: Journal    
DOI: None     Document Type: Review

References (103)

1. Moore B, Edie ES, Abram JH: On the treatment of diabetes mellitus by acid extracts of duodenal mucosa membrane. Biochem.J.28-38, 1906.
2. La Barre J: Sur les possibilites d'un traitment du diabetes par l'incretin. Bull Acad R Med Belg 12:620-634, 1932.
3. Mcintyre N, Turner DS, Holdsworth CD: New Interpretation of Oral Glucose Tolerance. Lancet 2:20-21, 1964.
4. Brown JC, Mutt V, Pederson RA: Further Purification of A Polypeptide Demonstrating Enterogastrone Activity. Journal of Physiology-London 209:57-64, 1970.
5. Dupre J, Ross SA, Watson D, Brown JC: Stimulation of Insulin-Secretion by Gastric Inhibitory Polypeptide in Man. Journal of Clinical Endocrinology and Metabolism 37:826-828, 1973.
6. Andersen DK, Elahi D, Brown JC, Tobin JD, Andres R: Oral Glucose Augmentation of Insulin-Secretion - Interactions of Gastric Inhibitory Polypeptide with Ambient Glucose and Insulin Levels. Journal of Clinical Investigation 62:152-161, 1978.
7. Elahi D, Andersen DK, Brown JC, Debas HT, Hershcopf RJ, Raizes GS, Tobin JD, Andres R: Pancreatic Alpha-Cell and Beta-Cell Responses to GIP Infusion in Normal Man. American Journal of Physiology 237:E185-E191, 1979.
8. Brown JC: Gastric Inhibitory Polypeptide. New York, Springer-Verlag, 1982,.
9. Maxwell V, Shulkes A, Brown JC, Solomon TE, Walsh JH, Grossman MI: Effect of Gastric-Inhibitory Polypeptide on Pentagastrin-Stimulated Acid-Secretion in Man. Digestive Diseases and Sciences 25:113-116, 1980.
10. Creutzfeldt W: Incretin Concept Today. Diabetologia 16:75-85, 1979.
11. Lauritsen KB, Moody AJ, Christensen KC, Jensen SL: Gastric-Inhibitory Polypeptide (GIP) and Insulin Release After Small Bowel Resection in Man. Scandinavian Journal of Gastroenterology 15:833-840, 1980.
12. Bell GI, Sanchez PR, Laybourn PJ, Najarian RC: Exon duplication and divergence in the human preproglucagon gene. Nature 304:368-371, 1983.
13. Novak U, Wilks A, Buell G, Mcewen S: Identical Messenger-Rna for Preproglucagon in Pancreas and Gut. European Journal of Biochemistry 164:553-558, 1987.
14. Mojsov S, Heinrich G, Wilson IB, Ravazzola M, Orci L, Habener JF: Preproglucagon Gene-Expression in Pancreas and Intestine Diversifies at the Level of Posttranslational Processing. Journal of Biological Chemistry 261:11880-11889, 1986.
15. Ørskov C, Holst JJ, Knuhtsen S, Baldissera FG, Poulsen SS, Nielsen OV: Glucagon-like peptides GLP-1 and GLP-2, predicted products of the glucagon gene, are secreted separately from pig small intestine but not pancreas. Endocrinology 119:1467-1475, 1986.
16. Ørskov C, Holst JJ, Poulsen SS, Kirkegaard P: Pancreatic and intestinal processing of proglucagon in man. Diabetologia 30:874-881, 1987.
17. Ørskov C, Andreasen J, Holst JJ: All products of proglucagon are elevated in plasma from uremic patients. J.Clin.Endocrinol.Metab. 74:379-384, 1992.
18. Ørskov 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. 264:12826-12829, 1989
19. Thim L, Moody AJ: The Primary Structure of Porcine Glicentin (Proglucagon). Regulatory Peptides 2:139-150, 1981
20. Holst JJ, Ørskov C, Nielsen OV, Schwartz TW: Truncated glucagon-like peptide I, an insulin-releasing hormone from the distal gut. FEBS Lett. 211:169-174, 1987
21. Mojsov S, Weir GC, Habener JF: Insulinotropin - Glucagonlike Peptide-I (7-37) Co-Encoded in the Glucagon Gene Is A Potent Stimulator of Insulin Release in the Perfused Rat Pancreas. Journal of Clinical Investigation 79:616-619, 1987.
22. Drucker DJ: Glucagon-like peptide 2. Journal of Clinical Endocrinology and Metabolism 86:1759-1764, 2001.
23. Creutzfeldt W, Ebert R: New developments in the incretin concept. Diabetologia 28:565-573, 1985.
24. Creutzfeldt W, Nauck M: Gut hormones and diabetes mellitus. Diabetes Metab.Rev. 8:149-177, 1992.
25. Kreymann B, Williams G, Ghatei MA, Bloom SR: Glucagon-like peptide-1 7-36: a physiological incretin in man. Lancet 2:1300-1304, 1987.
26. Perley MJ, Kipnis DM: Plasma Insulin Responses to Oral and Intravenous Glucose - Studies in Normal and Diabetic Subjects. Journal of Clinical Investigation 46:1954-1962, 1967.
27. Morgan LM: The role of gastrointestinal hormones in carbohydrate and lipid metabolism and homeostasis: effects of gastric inhibitory polypeptide and glucagon-like peptide-1. Biochem.Soc.Trans. 26:216-222, 1998.
28. O'Harte FP, Abdel-Wahab YH, Conlon JM, Flatt PR: Amino terminal glycation of gastric inhibitory polypeptide enhances its insulinotropic action on clonal pancreatic B-cells. Biochim.Biophys.Acta 1425:319-327, 1998.
29. 2+-induced secretion in rat alpha-cells by a protein kinase A-mediated mechanism. Diabetes 46:792-800, 1997.
30. Miyawaki K, Yamada Y, Ban N, Ihara Y, Tsukiyama K, Zhou HY, Fujimoto S, Oku A, Tsuda K, Toyokuni S, Hiai H, Mizunoya W, Fushiki T, Holst JJ, Makino M, Tashita A, Kobara Y, Tsubamoto Y, Jinnouchi T, Jomori T, Seino Y: Inhibition of gastric inhibitory polypeptide signaling prevents obesity. Nature Medicine 8:738-742, 2002.
31. Yip RG, Boylan MO, Kieffer TJ, Wolfe MM: Functional GIP receptors are present on adipocytes. Endocrinology 139:4004-4007, 1998.
32. Elliott RM, Morgan LM, Tredger JA, Deacon S, Wright J, Marks V: 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. J.Endocrinol. 138:159-166, 1993.
33. Øskov C, Wettergren A, Holst JJ: Secretion of the incretin hormones glucagon-like peptide-1 and gastric inhibitory polypeptide correlates with insulin secretion in normal man throughout the day. Scand.J.Gastroenterol. 31:665-670, 1996
34. Layer P, Holst JJ, Grandt D, Goebell H: Ileal release of glucagon-like peptide-1 (GLP-1). Association with inhibition of gastric acid secretion in humans. Dig.Dis.Sci. 40:1074-1082, 1995.
35. Gromada J, Holst JJ, Rorsman P: Cellular regulation of islet hormone secretion by the incretin hormone glucagon-like peptide 1. Pflugers Arch. 435:583-594, 1998.
36. Fehmann HC, Goke R, Goke B: Cell and molecular biology of the incretin hormones glucagon-like peptide-I and glucose-dependent insulin releasing polypeptide. Endocr.Rev. 16:390-410, 1995.
37. Stoffers DA, Kieffer TJ, Hussain MA, Drucker DJ, Bonner-Weir S, Habener JF, Egan JM: Insulinotropic glucagon-like peptide 1 agonists stimulate expression of homeodomain protein IDX-1 and increase islet size in mouse pancreas. Diabetes 49:741-748, 2000.
38. Nauck MA, Heimesaat MM, Behle K, Holst JJ, Nauck MS, Ritzel R, Hufner M, Schmiegel WH: Effects of glucagon-like peptide 1 on counterregulatory hormone responses, cognitive functions, and insulin secretion during hyperinsulinemic, stepped hypoglycemic clamp experiments in healthy volunteers. Journal of Clinical Endocrinology and Metabolism 87:1239-1246, 2002.
39. Hvidberg A, Nielsen MT, Hilsted J, Øskov C, Holst JJ: Effect of glucagon-like peptide-1 (proglucagon 78-107amide) on hepatic glucose production in healthy man. Metabolism 43:104-108, 1994.
40. Larsson H, Holst JJ, Ahren B: Glucagon-like peptide-1 reduces hepatic glucose production indirectly through insulin and glucagon in humans. Acta Physiol.Scand. 160:413-422, 1997.
41. 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.Sci. 38:665-673, 1993.
42. Willms B, Werner J, Holst JJ, Øskov C, Creutzfeldt W, Nauck MA: Gastric emptying, glucose responses, and insulin secretion after a liquid test meal: effects of exogenous glucagon-like peptide-1 (GLP-1)-(7-36) amide in type 2 (noninsulin-dependent) diabetic patients. J.Clin.Endocrinol. Metab. 81:327-332, 1996.
43. Flint A, Raben A, Astrup A, Holst JJ: Glucagon-like peptide 1 promotes satiety and suppresses energy intake in humans. J.Clin.Invest. 101:515-520, 1998.
44. Gutzwiller JP, Drewe J, Goke B, Schmidt H, Rohrer B, Lareida J, Beglinger C: Glucagon-like peptide-1 promotes satiety and reduces food intake in patients with diabetes mellitus type 2. American Journal of Physiology-Regulatory Integrative and Comparative Physiology 276: R1541-R1544, 1999.
45. Edwards CMB, Todd JF, Mahmoudi M, Wang ZL, Wang RM, Ghatei MA, Bloom SR: Glucagon-like peptide 1 has a physiological role in the control of postprandial glucose in humans - Studies with the antagonist exendin 9-39. Diabetes 48:86-93, 1999.
46. Scrocchi LA, Brown TJ, MaClusky N, Brubaker PL, Auerbach AB, Joyner AL, Drucker DJ: Glucose intolerance but normal satiety in mice with a null mutation in the glucagon-like peptide 1 receptor gene. Nat.Med. 2:1254-1258, 1996.
47. Miyawaki K, Yamada Y, Yano H, Niwa H, Ban N, Ihara Y, Kubota A, Fujimoto S, Kajikawa M, Kuroe A, Tsuda K, Hashimoto H, Yamashita T, Jomori T, Tashiro F, Miyazaki J, Seino Y: Glucose intolerance caused by a defect in the entero-insular axis: a study in gastric inhibitory polypeptide receptor knockout mice. Proc.Natl.Acad.Sci.U.S.A 96:14843-14847, 1999.
48. Jia X, Brown JC, Ma P, Pederson RA, Mcintosh CHS: Effects glucose-dependent insulinotropic polypeptide and glucagon-like peptide-I-(7-36) on insulin-secretion. American Journal of Physiology-Endocrinology and Metabolism 31:E645-E651, 1995.
49. Elahi D, McAloon-Dyke M, Fukagawa NK, Meneilly GS, Sclater AL, Minaker KL, Habener JF, Andersen DK: The insulinotropic actions of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (7-37) in normal and diabetic subjects. Regul.Pept. 51:63-74, 1994.
50. Nauck MA, Bartels E, Øskov C, Ebert R, Creutzfeldt W: Additive insulinotropic effects of exogenous synthetic human gastric inhibitory polypeptide and glucagon-like peptide-1-(7-36) amide infused at nearphysiological insulinotropic hormone and glucose concentrations. J.Clin.Endocrinol.Metab. 76:912-917, 1993.
51. Toft-Nielsen M, Madsbad S, Holst JJ: Exaggerated secretion of glucagon-like peptide-1 (GLP-1) could cause reactive hypoglycaemia. Diabetologia 41:1180-1186, 1998.
52. Nauck M, Schmidt WE, Ebert R, Strietzel J, Cantor P, Hoffmann G, Creutzfeldt W: Insulinotropic properties of synthetic human gastric inhibitory polypeptide in man: interactions with glucose, phenylalanine, and cholecystokinin-8. J.Clin.Endocrinol.Metab. 69:654-662, 1989.
53. Nauck M, Stockmann F, Ebert R, Creutzfeldt W: Reduced incretin effect in type 2 (non-insulin-dependent) diabetes. Diabetologia 29:46-52, 1986.
54. Nauck MA, Homberger E, Siegel EG, Allen RC, Eaton RP, Ebert R, Creutzfeldt W: Incretin effects of increasing glucose loads in man calculated from venous insulin and C-peptide responses. J.Clin.Endocrinol. Metab 63:492-498, 1986.
55. Nauck MA, Kleine N, Øskov C, Holst JJ, 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 36:741-744, 1993.
56. Zander M, Madsbad S, Madsen JL, Holst JJ: 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 359: 824-830, 2002.
57. Vilsbøll T, Krarup T, Madsbad S, Holst JJ: No reactive hypoglycaemia in Type 2 diabetic patients after subcutaneous administration of GLP-1 and intravenous glucose. Diabet.Med 18:144-149, 2001.
58. Knop F, Vilsbøll T, Larsen S, Madsbad S, Holst JJ, Krarup T: No hypoglycaemia 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 26:2581-2587, 2003.
59. Deacon CF, Nauck MA, Toft-Nielsen MB, 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 44:1126-1131, 1995.
60. 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. J.Clin.Endocrinol.Metab 85:3575-3581, 2000.
61. Pederson RA, Kieffer TJ, Pauly R, Kofod H, Kwong J, McIntosh CH: The enteroinsular axis in dipeptidyl peptidase IV-negative rats. Metabolism 45:1335-1341, 1996.
62. Kieffer TJ, Mcintosh CHS, Pederson RA: Degradation of Glucose-Dependent Insulinotropic Polypeptide and Truncated Glucagon-Like Peptide-1 In-Vitro and In-Vivo by Dipeptidyl Peptidase-Iv. Endocrinology 136:3585-3596, 1995.
63. Mentlein R: Dipeptidyl-peptidase IV (CD26)-role in the inactivation of regulatory peptides. Regul.Pept. 85:9-24, 1999.
64. Brown JC, Dryburgh JR, Ross SA, Dupre J: Identification and actions of gastric inhibitory polypeptide. Recent.Prog.Horm.Res. 31:487-532, 1975.
65. Weir GC, Mojsov S, Hendrick GK, Habener,JF: Glucagonlike peptide I (7-37) actions on endocrine pancreas. Diabetes 38:338-342, 1989.
66. 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. 271:E458-E464, 1996.
67. Fukase N, Igarashi M, Takahashi H, Manaka H, Yamatani K, Daimon M, Tominaga M, Sasaki H: Hypersecretion of Truncated Glucagon-Like Peptide-1 and Gastric-Inhibitory Polypeptide in Obese Patients. Diabetic Medicine 10:44-49, 1993.
68. Fukase N, Manaka H, Sugiyama K, Takahashi H, Igarashi M, Daimon M, Yamatani K, Tominaga M, Sasaki H: Response of Truncated Glucagon-Like Peptide-1 and Gastric-Inhibitory Polypeptide to Glucose-Ingestion in Non-Insulin-Dependent Diabetes-Mellitus - Effect of Sulfonylurea Therapy. Acta Diabetologica 32:165-169, 1995.
69. Ranganath LR, Beety JM, Morgan LM, Wright JW, Howland R, Marks V: Attenuated GLP-1 secretion in obesity: Cause or consequence? Gut 38:916-919, 1996.
70. Vaag AA, Holst JJ, Vølund A, Beck NH: 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.J.Endocrinol. 135:425-432, 1996.
71. Naslund E, Hellstrom PM: Glucagon-like peptide-1 in the pathogenesis of obesity. Drug News & Perspectives 11:92-97, 1998.
72. Ørskov C, Jeppesen J, Madsbad S, Holst JJ: Proglucagon products in plasma of noninsulin-dependent diabetics and nondiabetic controls in the fasting state and after oral glucose and intravenous arginine. J.Clin.Invest 87:415-423, 1991.
73. 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.J.Endocrinol. 137:127-131, 1997.
74. Nauck MA, Heimesaat MM, Ørskov 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. 91:301-307, 1993.
75. Vilsbøll 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 50:609-613, 2001.
76. Lugari R, Dell'Anna C, Ugolotti D, Dei Cas A, Barilli AL, Zandomeneghi R, Marani B, Lotti M, Orlandini A, Gnudi A: Effect of nutrient ingestion on glucagon-like peptide 1 (7-36 amide) secretion in human type 1 and type 2 diabetes. Hormone and Metabolic Research 32:424-428, 2000.
77. Miholic J, Ørskov C, Holst JJ, Kotzerke J, Meyer HJ: Emptying of the gastric substitute, glucagon-like peptide-1 (GLP-1), and reactive hypoglycemia after total gastrectomy. Dig.Dis.Sci. 36:1361-1370, 1991.
78. Qualmann C, Nauck MA, Holst JJ, Ørskov C, Creutzfeldt W: Glucagonlike peptide 1 (7-36 amide) secretion in response to luminal sucrose from the upper and lower gut. A study using alpha-glucosidase inhibition (acarbose). Scand.J.Gastroenterol. 30:892-896, 1995.
79. Kong MF, Horowitz M: Gastric emptying in diabetes mellitus: relationship to blood-glucose control. Clin.Geriatr.Med 15:321-338, 1999.
80. Maddox A, Horowitz M, Wishart J, Collins P: Gastric and oesophageal emptying in obesity. Scand.J.Gastroenterol. 24:593-598, 1989.
81. Wisen O, Johansson C: Gastrointestinal function in obesity: motility, secretion, and absorption following a liquid test meal. Metabolism 41: 390-395, 1992.
82. Toft-Nielsen MB, Damholt MB, Madsbad S, Hilsted LM, Hughes TE, Michelsen BK, Holst JJ: Determinants of the impaired secretion of glucagon-like peptide-1 in type 2 diabetic patients. J.Clin.Endocrinol.Metab 86:3717-3723, 2001.
83. Vilsbøll T, Krarup T, Sonne J, Madsbad S, Vølund A, Juul AG, Holst JJ: Incretin Secretion in Relation to Meal Size and Body Weight in Healthy Subjects and People With Type 1 and Type 2 Diabetes Mellitus. J.Clin. Endocrinol.Metab 88:2706-2713, 2003.
84. Lugari R, Dei Cas A, Ugolotti D, Finardi L, Barilli AL, Ognibene C, Luciani A, Zandomeneghi R, Gnudi A: Evidence for early impairment of glucagon-like peptide 1-induced insulin secretion in human type 2 (non insulin-dependent) diabetes. Hormone and Metabolic Research 34:150-154, 2002.
85. Vilsbøll T, Agersø H, Krarup T, Holst JJ: Similar elimination rates of glucagon-like Peptide-1 in obese type 2 diabetic patients and healthy subjects. J.Clin.Endocrinol.Metab 88:220-224, 2003.
86. Nyholm B, Walker M, Gravholt CH, Shearing PA, Sturis J, Alberti KG, Holst JJ, Schmitz O: 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 42:1314-1323, 1999.
87. Pederson RA, Brown JC: Insulinotropic Action of Gastric Inhibitory Polypeptide in Perfused Isolated Rat Pancreas. Endocrinology 99:780-785, 1976.
88. Vilsbøll 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.Pept. 114:115-121, 2003.
89. Porte D: Banting lecture 1990. Beta-cells in type II diabetes mellitus. Diabetes 40:166-180, 1991.
90. Vilsbøll T, Toft-Nielsen MB, Krarup T, Madsbad S, Dinesen B, Holst JJ: Evaluation of beta-cell secretory capacity using glucagon-like peptide 1. Diabetes Care 23:807-812, 2000.
91. Kjems LL, Holst JJ, Vølund A, Madsbad S: The Influence of GLP-1 on Glucose-Stimulated Insulin Secretion: Effects on beta-Cell Sensitivity in Type 2 and Nondiabetic Subjects. Diabetes 52:380-386, 2003.
92. Ward WK, Bolgiano DC, McKnight B, Halter JB, Porte D: Diminished B cell secretory capacity in patients with noninsulin-dependent diabetes mellitus. J.Clin.Invest. 74:1318-1328, 1984.
93. Krarup T, Saurbrey N, Moody AJ, Kuhl C, Madsbad S: Effect of porcine gastric inhibitory polypeptide on beta-cell function in type I and type II diabetes mellitus. Metabolism 36:677-682, 1987.
94. Vilsbøll T, Krarup T, Madsbad S, Holst JJ: Defective amplification of the late phase insulin response to glucose by GIP in obese Type II diabetic patients. Diabetologia 45:1111-1119, 2002.
95. Vilsbøll T, Knop F, Krarup T, Johansen A, Madsbad S, Larsen S, Hansen T, Pedersen O, Holst JJ: The Pathophysiology of Diabetes Involves a Defective Amplification of the Late Phase Insulin Response to Glucose by GIP - Regardless of Etiology and Phenotype. J.Clin.Endocrinol.Metab. 88:4897-903, 2003.
96. Goke R, Trautmann ME, Haus E, Richter G, Fehmann HC, Arnold R, Goke B: Signal transmission after GLP-1(7-36)amide binding in RINm5F cells. Am.J.Physiol 257:G397-G401, 1989.
97. Gromada J, Rorsman P, Dissing S, Wulff BS: Stimulation of cloned human glucagon-like peptide 1 receptor expressed in HEK 293 cells induces cAMP-dependent activation of calcium-induced calcium release [published erratum appears in FEBS Lett 1996 Mar 4;381(3):262]. FEBS Lett. 373:182-186, 1995.
98. Gromada J, Dissing S, Bokvist K, Renstrom E, Frokjaer JJ, Wulff BS, Rorsman P: Glucagon-like peptide I increases cytoplasmic calcium in insulin-secreting beta TC3-cells by enhancement of intracellular calcium mobilization. Diabetes 44:767-774, 1995.
99. 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 44:495-500, 1995.
100. Holst JJ, Gromada J, Nauck MA: The pathogenesis of NIDDM involves a defective expression of the GIP receptor. Diabetologia 40:984-986, 1997.
101. Lynn FC, Pamir N, Ng EHC, Mcintosh CHS, Kieffer TJ, Pederson RA: Defective glucose-dependent insulinotropic polypeptide receptor expression in diabetic fatty Zucker rats. Diabetes 50:1004-1011, 2001.
102. Kubota A, Yamada Y, Hayami T, Yasuda K, Someya Y, Ihara Y, Kagimoto S, Watanabe R, Taminato T, Tsuda K, Seino Y: 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 45:1701-1705, 1996.
103. Meier JJ, Hucking K, Holst JJ, Deacon,CF, Schmiegel,WH, Nauck,MA: Reduced insulinotropic effect of gastric inhibitory polypeptide in firstdegree relatives of patients with type 2 diabetes. Diabetes 50:2497-2504, 2001.