Enhancing incretin action for the treatment of type 2 diabetes

Diabetes Care

Volumn 26, Issue 10, 2003, Pages 2929-2940

  Drucker, Daniel J ^a  

^a UNIVERSITY OF TORONTO   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

CJC 1131; DIPEPTIDYL PEPTIDASE IV; DIPEPTIDYL PEPTIDASE IV INHIBITOR; EXENDIN 4; GASTRIC INHIBITORY POLYPEPTIDE; GLUCAGON LIKE PEPTIDE 1; GLUCAGON LIKE PEPTIDE 1 RECEPTOR; GLUCAGON LIKE PEPTIDE 1 RECEPTOR AGONIST; GLUCOSE; INCRETIN; INSULIN; LIRAGLUTIDE; METFORMIN; NN 211; SULFONYLUREA DERIVATIVE; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; CELL PROLIFERATION; CELL PROTECTION; CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; DOSE TIME EFFECT RELATION; DRUG ACTIVITY; DRUG MECHANISM; DRUG POTENCY; DRUG RECEPTOR BINDING; DRUG USE; ENZYME INHIBITION; EVALUATION; EXPERIMENTAL DIABETES MELLITUS; FOOD INTAKE; GASTROINTESTINAL SYMPTOM; GLUCAGON RELEASE; GLUCOSE BLOOD LEVEL; GLUCOSE METABOLISM; HUMAN; HYPOGLYCEMIA; INSULIN LIKE ACTIVITY; INSULIN RELEASE; MOUSE; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; PANCREAS ISLET BETA CELL; PEPTIDE ANALYSIS; PROTEIN DEGRADATION; REVIEW; RISK BENEFIT ANALYSIS; SIDE EFFECT; STOMACH EMPTYING;

ANTIGENS, CD26; DIABETES MELLITUS, TYPE 2; ENZYME INHIBITORS; GASTRIC INHIBITORY POLYPEPTIDE; GLUCAGON; GLUCAGON-LIKE PEPTIDE 1; HUMANS; PEPTIDE FRAGMENTS; PROTEIN PRECURSORS;

EID: 0141446228     PISSN: 01495992     EISSN: None     Source Type: Journal    
DOI: 10.2337/diacare.26.10.2929     Document Type: Review

References (172)

1. Elrick H, Stimmler L, Hlad CJ, Arai Y: Plasma insulin responses to oral and intravenous glucose administration. J Clin Endocrinol Metab 24:1076-1082, 1964
2. McIntyre N, Holdsworth CD, Turner DS: Intestinal factors in the control of insulin secretion. J Clin Endocrinol Metab 25:1317-1324, 1965
3. Dupre J, Beck JC: Stimulation of release of insulin by an extract of intestinal mucosa. Diabetes 15:555-559, 1966
4. Takeda J, Seino Y, Tanaka K, Fukumoto H, Kayano T, Takahashi H, Mitani T, Kurono M, Suzuki T, Tobe T, et al: Sequence of an intestinal cDNA encoding human gastric inhibitory polypeptide precursor. Proc Natl Acad Sci U S A 84: 7005-7008, 1987
5. Bell GI, Sanchez-Pescador R, Laybourn PJ, Najarian RC: Exon duplication and divergence in the human preproglucagon gene. Nature 304:368-371, 1983
6. Orskov C, Wettergren A, Holst JJ: Biological effects and metabolic rates of glucagon-like peptide 1(7-36)amide and glucagon-like peptide 1(7-37) in healthy subjects are indistinguishable. Diabetes 42:658-661, 1993
7. Nauck MA, Kleine N, Orskov 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
8. Orskov C, Rabenhoj L, Wettergren A, Kofod H, Holst JJ: Tissue and plasma concentrations of amidated and glycine-extended glucagon-like peptide 1 in humans. Diabetes 43:535-539, 1994
9. Herrmann C, Goke R, Richter G, Fehmann HC, Arnold R, Goke B: Glucagon-like peptide-1 and glucose-dependent insulin-releasing polypeptide plasma levels in response to nutrients. Digestion 56:117-126, 1995
10. 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
11. Rocca AS, Brubaker PL: Role of the vagus nerve in mediating proximal nutrient-induced glucagon-like peptide-1 secretion. Endocrinology 140:1687-1694, 1999
12. Anini Y, Hansotia T, Brubaker PL: Muscarinic receptors control postprandial release of glucagon-like peptide-1: in vivo and in vitro studies in rats. Endocrinology 143:2420-2426, 2002
13. 2-terminus in type 2 diabetic patients and in healthy subjects. Diabetes 44:1126-1131, 1995
14. Deacoa 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
15. Kieffer TJ, McIntosh CH, Pederson RA: Degradation of glucose-dependent insulinotropic polypeptide and truncated glucagon-like peptide 1 in vitro and in vivo by dipeptidyl peptidase IV. Endocrinology 136:3585-3596, 1995
16. Mentlein R, Gallwitz B, Schmidt WE: Dipeptidyl-peptidase IV hydrolyses gastric inhibitory polypeptide, glucagon-like peptide-1(7-36)amide, peptide histidine methionine and is responsible for their degradation in human serum. Eur J Biochem 214:829-835, 1993
17. Vilsboll T, Agerso H, Krarup T, Holst JJ: Similar elimination rates of glucagon-like peptide-1 in obese type 2 diabetic patients and healthy subjects. J Clin Endocrinol Metab 88:220-224, 2003
18. Gault VA, Parker JC, Harriott P, Flatt PR, O'Harte FP: Evidence that the major degradation product of glucose-dependent insulinotropic polypeptide, GIP(3-42), is a GIP receptor antagonist in vivo. J Endocrinol 175:525-533, 2002
19. Knudsen LB, Pridal L: Glucagon-like peptide-1-(9-36) amide is a major metabolite of glucagon-like peptide-1-(7-36)amide after in vivo administration to dogs and it acts as an antagonist on the pancreatic receptor. Eur J Pharmacol 318:429-435, 1996
20. Deacon CF, Plamboeck A, Moller S, Holst JJ: GLP-1-(9-36) amide reduces blood glucose in anesthetized pigs by a mechanism that does not involve insulin secretion. Am J Physiol 282:E873-E879, 2002
21. Vahl TP, Paty BW, Fuller BD, Prigeon RL, D'Alessio DA: Effects of GLP-1-(7-36)NH(2), GLP-1-(7-37), and GLP-1-(9-36)NH(2) on intravenous glucose tolerance and glucose-induced insulin secretion in healthy humans. J Clin Endocrinol Metab 88:1772-1779, 2003
22. Vilsboll T, Krarup T, Deacon CF, Madsbad S, Holst JJ: Reduced postprandial concentrations of intact biologically active glucagon-like peptide 1 in type 2 diabetic patients. Diabetes 50:609-613, 2001
23. 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. Horm Metab Res 34:150-154, 2002
24. Rask E, Olsson T, Soderberg S, Johnson O, Seckl J, Holst JJ, Ahren B: Impaired incretin response after a mixed meal is associated with insulin resistance in non-diabetic men. Diabetes Care 24:1640-1645, 2001
25. Yip RG, Wolfe MM: GIP biology and fat metabolism. Life Sci 66:91-103, 2000
26. Trumper A, Trumper K, Trusheim H, Arnold R, Goke B, Horsch D: Glucose-dependent insulinotropic polypeptide is a growth factor for beta (INS-1) cells by pleiotropic signaling. Mol Endocrinol 15: 1559-1570, 2001
27. Trumper A, Trumper K, Horsch D: Mechanisms of mitogenic and anti-apoptotic signaling by glucose-dependent insulinotropic polypeptide in beta(INS-1)-cells. J Endocrinol 174:233-246, 2002
28. Gelling RW, Coy DH, Pederson RA, Wheeler MB, Hinke S, Kwan T, McIntosh CH: GIP(6-30amide) contains the high affinity binding region of GIP and is a potent inhibitor of GIP1-42 action in vitro. Regul Pept 69:151-154, 1997
29. Tseng CC, Zhang XY, Wolfe MM: Effect of GIP and GLP-1 antagonists on insulin release in the rat. Am J Physiol 276: E1049-E1054, 1999
30. Gault VA, O'Harte FP, Harriott P, Mooney MH, Green BD, Flatt PR: Effects of the novel (Pro[3])GIP antagonist and exendin(9-39)amide on GIP- and GLP-1-induced cyclic AMP generation, insulin secretion and postprandial insulin release in obese diabetic (ob/ob) mice: evidence that GIP is the major physiological incretin. Diabetologia 46:222-230, 2003
31. Lewis JT, Dayanandan B, Habener JF, Kieffer TJ: Glucose-dependent insulinotropic polypeptide confers early phase insulin release to oral glucose in rats: demonstration by a receptor antagonist. Endocrinology 141:3710-3716, 2000
32. Baggio L, Kieffer TJ, Drucker DJ: GLP-1 but not GIP regulates fasting and non-enteral glucose clearance in mice. Endocrinology 141:3703-3709, 2000
33. 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 enteroinsular axis: a study in gastric inhibitory polypeptide receptor knockout mice. Proc Natl Acad Sci U S A 96:14843-14847, 1999
34. Miyawaki K, Yamada Y, Ban N, Ihara Y, Tsukiyama K, Zhou H, 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. Nat Med 8: 738-742, 2002
35. Tseng CC, Boylan MO, Jarboe LA, Usdin TB, Wolfe MM: Chronic desensitization of the glucose-dependent insulinotropic polypeptide receptor in diabetic rats. Am J Physiol 270:E661-E666, 1996
36. Lynn FC, Pamir N, Ng EH, McIntosh CH, Kieffer TJ, Pederson RA: Defective glucose-dependent insulinotropic polypeptide receptor expression in diabetic fatty Zucker rats. Diabetes 50:1004-1011, 2001
37. O'Harte FP, Mooney MH, Kelly CM, Flatt PR: Improved glycaemic control in obese diabetic ob/ob mice using N-terminally modified gastric inhibitory polypeptide. J Endocrinol 165:639-648, 2000
38. O'Harte FP, Gault VA, Parker JC, Harriott P, Mooney MH, Bailey CJ, Flatt PR: Improved stability, insulin-releasing activity and antidiabetic potential of two novel N-terminal analogues of gastric inhibitory polypeptide: N-acetyl-GIP and pGlu-GIP. Diabetologia 45:1281-1291, 2002
39. Hinke SA, Gelling RW, Pederson RA, Manhart S, Nian C, Demuth HU, McIntosh CH: Dipeptidyl peptidase IV-resistant [D-Ala(2)]glucose-dependent insulinotropic polypeptide (GIP) improves glucose tolerance in normal and obese diabetic rats. Diabetes 51:652-661, 2002
40. Jones IR, Owens DR, Luzio S, Hayes TM: Glucose dependent insulinotropic polypeptide (GIP) infused intravenously is insulinotropic in the fasting state in type 2 (non-insulin dependent) diabetes mellitus. Horm Metab Res 21:23-26, 1989
41. Nauck M, Stockmann F, Ebert R, Creutzfeldt W: Reduced incretin effect in type 2 (non-insulin-dependent) diabetes. Diabetologia 29:46-52, 1986
42. 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
43. Jones IR, Owens DR, Vora J, Luzio SD, Hayes TM: A supplementary infusion of glucose-dependent insulinotropic polypeptide (GIP) with a meal does not significantly improve the beta cell response or glucose tolerance in type 2 diabetes mellitus. Diabetes Res Clin Pract 7:263-269, 1989
44. Jones IR, Owens DR, Moody AJ, Luzio SD, Morris T, Hayes TM: The effects of glucose-dependent insulinotropic polypeptide infused at physiological concentrations in normal subjects and type 2 (non-insulin-dependent) diabetic patients on glucose tolerance and B-cell secretion. Diabetologia 30:707-712, 1987
45. 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
46. Meneilly GS, Bryer-Ash M, Elahi D: The effect of glyburide on beta-cell sensitivity to glucose-dependent insulinotropic polypeptide. Diabetes Care 16:110-114, 1993
47. Vilsboll 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
48. Meier JJ, Hucking K, Holst JJ, Deacon CF, Schmiegel WH, Nauck MA: Reduced insulinotropic effect of gastric inhibitory polypeptide in first-degree relatives of patients with type 2 diabetes. Diabetes 50:2497-2504, 2001
49. Mojsov S, Weir GC, Habener JF: Insulinotropin: Glucagon-like peptide I (7-37) co-encoded in the glucagon gene is a potent stimulator of insulin release in the perfused rat pancreas. J Clin Invest 79:616-619, 1987
50. Kreymann B, Ghatei MA, Williams G, Bloom SR: Glucagon-like peptide-1 7-36: a physiological incretin in man. Lancet ii:1300-1304, 1987
51. Orskov C, Holss JJ, Nielsen OV: Effect of truncated glucagon-like peptide-1 [proglucagon-(78-107) amide] on endocrine secretion from pig pancreas, antrum, and nonantral stomach. Endocrinology 123:2009-2013, 1988
52. Drucker DJ, Philippe J, Mojsov S, Chick WL, Habener JF: Glucagon-like peptide I stimulates insulin gene expression and increases cyclic AMP levels in a rat islet cell line. Proc Natl Acad Sci U S A 84: 3434-3438, 1987
53. Matsuyama T, Komatsu R, Namba M, Watanabe N, Itoh H, Tarui S: Glucagon-like peptide-1 (7-36 amide): a potent glucagonostatic and insulinotropic hormone. Diabetes Res Clin Pract 5:281-284, 1988
54. Weir GC, Mojsov S, Hendrick GK, Habener JF: Glucagon-like peptide 1(7-37) actions on endocrine pancreas. Diabetes 38:338-342, 1989
55. 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
56. Turton MD, O'Shea D, Gunn I, Beak SA, Edwards CMB, Meeran K, Choi SJ, Taylor GM, Heath MM, Lambert PD, Wilding JPH, Smith DM, Ghatei MA, Herbert J, Bloom SR: A role for glucagon-like peptide-1 in the central regulation of feeding. Nature 379:69-72, 1996
57. Meeran K, O'Shea D, Edwards CM, Turton MD, Heath MM, Gunn I, Abusnana S, Rossi M, Small CJ, Goldstone AP, Taylor GM, Sunter D, Steere J, Choi SJ, Ghatei MA, Bloom SR: Repeated intracerebroventricular administration of glucagon-like peptide-1-(7-36) amide or exendin-(9-39) alters body weight in the rat. Endocrinology 140:244-250, 1999
58. Davis HR Jr, Mullins DE, Pines JM, Hoos LM, France CF, Compton DS, Graziano MP, Sybertz EJ, Strader CD, Van Heek M: Effect of chronic central administration of glucagon-like peptide-1 (7-36) amide on food consumption and body weight in normal and obese rats. Obes Res 6:147-156, 1998
59. Szayna M, Doyle ME, Betkey JA, Holloway HW, Spencer RG, Greig NH, Egan JM: Exendin-4 decelerates food intake, weight gain, and fat deposition in Zucker rats. Endocrinology 141:1936-1941, 2000
60. Larsen PJ, Fledelius C, Knudsen LB, 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 50:2530-2539, 2001
61. Donahey JCK, Van Dijk G, Woods SC, Seeley RJ: Intraventricular GLP-1 reduces short- but not long-term food intake or body weight in lean and obese rats. Brain Res 779:75-83, 1998
62. Thiele TE, Van Dijk G, Campfield LA, Smith FJ, Burn P, Woods SC, Bernstein H, Seeley RJ: Central infusion of GLP-1, but not leptin, produces conditioned taste aversion in rats. Am J Physiol 272: R726-R730, 1997
63. Seeley RJ, Blake K, Rushing PA, Benoit S, Eng J, Woods SC, D'Alessio D: The role of CNS glucagon-like peptide-1 (7-36) amide receptors in mediating the visceral illness effects of lithium chloride. J Neurosci 20:1616-1621, 2000
64. Rinaman L: A functional role for central glucagon-like peptide-1 receptors in lithium chloride-induced anorexia. Am J Physiol 277:R1537-R1540, 1999
65. van Dijk G, Thiele TE: Glucagon-like peptide-1 (7-36) amide: a central regulator of satiety and interoceptive stress. Neuropeptides 33:406-414, 1999
66. Kinzig KP, D'Alessio DA, Seeley RJ: The diverse roles of specific GLP-1 receptors in the control of food intake and the response to visceral illness. J Neurosci 22: 10470-10476, 2002
67. Holz GGt, Kuhtreiber WM, Habener JF: Pancreatic beta-cells are rendered glucose-competent by the insulinotropic hormone glucagon-like peptide-1(7-37). Nature 361:362-365, 1993
68. Dachicourt N, Serradas P, Bailbe D, Kergoat M, Doare L, Portha B: Glucagon-like peptide-1(7-36)-amide confers glucose sensitivity to previously glucose-incompetent beta-cells in diabetic rats: in vivo and in vitro studies J Endocrinol 155: 369-376, 1997
69. Xu G, Stoffers DA, Habener JF, Bonner-Weir S: Exendin-4 stimulates both β-cell replication and neogenesis, resulting in increased β-cell mass and improved glucose tolerance in diabetic rats. Diabetes 48:2270-2276, 1999
70. Li Y, Hansotia T, Yusta B, Ris F, Halban PA, Drucker DJ: Glucagon-like peptide-1 receptor signaling modulates beta cell apoptosis. J Biol Chem 278:471-478, 2003
71. Drucker DJ: Glucagon-like peptides: regulators of cell proliferation, differentiation and apoptosis. Mol Endocrinol 17: 161-171, 2003
72. Abraham EJ, Leech CA, Lin JC, Zulewski H, Habener JF: Insulinotropic hormone glucagon-like peptide-1 differentiation of human pancreatic islet-derived progenitor cells into insulin-producing cells. Endocrinology 143:3152-3161, 2002
73. Hardikar AA, Wang XY, Williams LJ, Kwok J, Wong R, Yao M, Tuch BE: Functional maturation of fetal porcine beta-cells by glucagon-like peptide 1 and cholecystokinin. Endocrinology 143:3505-3514, 2002
74. Movassat J, Beattie GM, Lopez AD, Hayek A: Exendin 4 up-regulates expression of PDX 1 and hastens differentiation and maturation of human fetal pancreatic cells. J Clin Endocrinol Metab 87:4775-4781, 2002
75. Tourrel C, Bailbe D, Meile M-J, Kergoat M, Portha B: Glucagon-like peptide 1 and exendin-4 stimulate β-cell neogenesis in streptozotocin-treated newborn rats resulting in persistently improved glucose homeostasis at adult age. Diabetes 50:1562-1570, 2001
76. Perfetti R, Zhou J, Doyle ME, Egan JM: Glucagon-like peptide-1 induces cell proliferation and pancreatic-duodenum homeobox-1 expression and increases endocrine cell mass in the pancreas of old, glucose-intolerant rats. Endocrinology 141:4600-4605, 2000
77. Stoffers DA, Desai BM, DeLeon DD, Simmons RA: Neonatal exendin-4 prevents the development of diabetes in the intra-uterine growth retarded rat. Diabetes 52: 734-740, 2003
78. Wang Q, Brubaker PL: Glucagon-like peptide-1 treatment delays the onset of diabetes in 8 week-old db/db mice. Diabetologia 45:1263-1273, 2002
79. Tourrel C, Bailbe D, Lacorne M, Meile MJ, Kergoat M, Portha B: Persistent improvement of type 2 diabetes in the Goto-Kakizaki rat model by expansion of the β-cell mass during the prediabetic period with glucagon-like peptide 1 or exendin-4. Diabetes 51:1443-1452, 2002
80. Edvell A, Lindstrom P: Initiation of increased pancreatic islet growth in young normoglycemic mice (Umea +/?). Endocrinology 140:778-783, 1999
81. Rolin B, Larsen MO, Gotfredsen CF, Deacon CF, Carr RD, Wilken M, Knudsen LB: The long-acting GLP-1 derivative NN2211 ameliorates glycemia and increases beta-cell mass in diabetic mice. Am J Physiol Endocrinol Metab 283: E745-E752, 2002
82. Kim J-G, Bagglo LL, Bridon DP, Castaigne J-P, Robitaille MF, Jette L, Benquet C, Drucker DJ: Development and characterization of a GLP-1-albumin conjugate which retains the ability to activate the GLP-1 receptor in vivo. Diabetes 52:751-759, 2003
83. Farilla L, Hui H, Bertolotto C, Kang E, Bulotta A, Di Mario U, Perfetti R: Glucagon-like peptide-1 promotes islet cell growth and inhibits apoptosis in Zucker diabetic rats. Endocrinology 143:4397-4408, 2002
84. Hui H, Nourparvar A, Zhao X, Perfetti R: Glucagon-like peptide-1 inhibits apoptosis of insulin-secreting cells via a cyclic 5′-adenosine monophosphate-dependent protein kinase A- and a phosphatidylinositol 3-kinase-dependent pathway. Endocrinology 144:1444-1455, 2003
85. Kolligs F, Fehmann H-C, Goke R, Goke B: Reduction of the incretin effect in rats by the glucagon-like peptide 1 receptor antagonist exendin (9-39) amide. Diabetes 44:16-19, 1995
86. Wang Z, Wang RM, Owji AA, Smith DM, Ghatei MA, Bloom SR: Glucagon-like peptide 1 is a physiological incretin in rat. J Clin Invest 95:417-421, 1995
87. D'alessio DA, Vogel R, Prigeon R, Laschansky E, Koerker D, Eng J, Ensinck JW: Elimination of the action of glucagon-like peptide 1 causes an impairment of glucose tolerance after nutrient ingestion by healthy baboons. J Clin Invest 97: 133-138, 1996
88. Imeryuz N, Yegen BC, Bozkurt A, Coskun T, Villanueva-Pennacarrillo ML, Ulusoy NB: Glucagon-like peptide-1 inhibits gastric emptying via vagal afferent-mediated central mechanisms. Am J Physiol 273:G920-G927, 1997
89. Schirra J, Sturm K, Leicht P, Arnold R, Goke B, Katschinski M: Exendin(9-39)amide is an antagonist of glucagon-like peptide-1(7-36)amide in humans. J Clin Invest 101:1421-1430, 1998
90. Edwards CM, Todd JF, Mahmoudi M, Wang Z, 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
91. Scrocchi LA, Marshall BA, Cook SM, Brubaker PL, Drucker DJ: Glucose homeostasis in mice with disruption of GLP-1 receptor signaling. Diabetes 47: 632-639, 1998
92. Gros R, You X, Baggio LL, Kabir MG, Sadi A-M, Mungrue IN, Parker TG, Huang Q, Drucker DJ, Husain M: Cardiac function in mice lacking the glucagon-like peptide-1 receptor. Endocrinology 144:2242-2252, 2003
93. Goldstone AP, Mercer JG, Gunn I, Moar KM, Edwards CMB, Rossi M, Howard JK, Rasheed S, Turton MD, Small C, Heath MM, O'Shea D, Steere J, Meeran K, Ghatei MA, Hoggard N, Bloom SR: Leptin interacts with glucagon-like peptide-1 neurons to reduce food intake and body weight in rodents. FEBS Lett 415: 134-138, 1997
94. Scrocchi LA, Brown TJ, Drucker DJ: Leptin sensitivity in non-obese GLP-1 receptor -/- mice. Diabetes 46:2029-2034, 1997
95. Scrocchi LA, Hill ME, Saleh J, Perkins B, Drucker DJ: Elimination of GLP-1R signaling does not modify weight gain and islet adaptation in mice with combined disruption of leptin and GLP-1 action. Diabetes 49:1552-1560, 2000
96. 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 receptor gene. Nat Med 2:1254-1258, 1996
97. Scrocchi LA, Drucker DJ: Effects of aging and a high fat diet on body weight and glucose control in GLP-1R-/- mice. Endocrinology 139:3127-3132, 1998
98. Ling Z, Wu D, Zambre Y, Flamez D, Drucker DJ, Pipeleers DG, Schuit FC: Glucagon-like peptide 1 receptor signaling influences topography of islet cells in mice. Virchows Arch 438:382-387, 2001
99. De Leon DD, Deng S, Madani R, Ahima RS, Drucker DJ, Stoffers DA: Role of endogenous glucagon-like peptide-1 in islet regeneration following partial pancreatectomy. Diabetes 52:365-371, 2003
100. Wang Y, Perfetti R, Greig NH, Holloway HW, DeOre KA, Montrose-Rafizadeh C, Elahi D, Egan JM: Glucagon-like peptide-1 can reverse the age-related decline in glucose tolerance in rats. J Clin Invest 99:2883-2889, 1997
101. Shen HQ, Roth MD, Peterson RG: The effect of glucose and glucagon-like peptide-1 stimulation on insulin release in the perfused pancreas in a non-insulin-dependent diabetes mellitus animal model. Metabolism 47:1042-1047, 1998
102. Hargrove DM, Nardone NA, Persson LM, Parker JC, Stevenson RW: Glucose-dependent action of glucagon-like peptide-1(7-37) in vivo during short- or long-term administration. Metabolism 44:1231-1237, 1995
103. Jia X, Elliott R, Kwok YN, Pederson RA, McIntosh CHS: Altered glucose dependence of glucagon-like peptide 1(7-36)-induced insulin secretion from the Zucker (fa/fa) rat pancreas. Diabetes 44: 495-500, 1995
104. Young AA, Gedulin BR, Bhavsar S, Bodkin N, Jodka C, Hansen B, Denaro M: 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 48:1026-1034, 1999
105. Greig NH, Holloway HW, De Ore KA, Jani D, Wang Y, Zhou J, Garant MJ, Egan JM: Once daily injection of exendin-4 to diabetic mice achieves long-term beneficial effects on blood glucose concentrations. Diabetologia 42:45-50, 1999
106. Ribel U, Larsen M, Rolin B, Carr R, Wilken M, Sturis J, Westergaard L, Deacon C, Knudsen L: NN2211: a long-acting glucagon-like peptide-1 derivative with anti-diabetic effects in glucose-intolerant pigs. Eur J Pharmacol 451:217-225, 2002
107. Hui H, Farilla L, Merkel P, Perfetti R: The short half-life of glucagon-like peptide-1 in plasma does not reflect its long-lasting beneficial effects. Eur J Endocrinol 146: 863-869, 2002
108. Qualmann C, Nauck MA, Holst JJ, 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 32:13-16, 1995
109. Nauck MA, Heimesaat MM, Orskov C, Holst JJ, Ebert R, Creutzfeldt W: Preserved incretin activity of glucagon-like peptide 1 [7-36 amide] but not of synthetic human gastric inhibitory polypeptide in patients with type-2 diabetes mellitus. J Clin Invest 91:301-307, 1993
110. Schjoldager BTG, Mortensen PE, Christiansen J, Orskov C, Holst JJ: GLP-1 (glucagon-like peptide 1) and truncated GLP-1, fragments of human proglucagon, inhibit gastric acid secretion in humans. Dig Dis Sci 34:703-708, 1989
111. 2: a physiological inhibitor of gastric acid secretion in man. J Endocrinol 126:169-173, 1990
112. Nauck MA, Niedereichholz U, Ettler R, Holst JJ, Orskov C, Ritzel R, Schmiegel WH: Glucagon-like peptide 1 inhibition of gastric emptying outweighs its insulinotropic effects in healthy humans. Am J Physiol 273:E981-E988, 1997
113. Nauck MA: Is glucagon-like peptide 1 an incretin hormone? Diabetologia 42:373-379, 1999
114. Gutniak M, Orskov C, Holst JJ, Ahren B, Efendic S: Antidiabetogenic effect of glucagon-like peptide-1 (7-36)amide in normal subjects and patients with diabetes mellitus. N Engl J Med 326:1316-1322, 1992
115. Dupre J, Behme MT, Hramiak IM, McFarlane P, Williamson MP, Zabel P, McDonald TJ: Glucagon-like peptide 1 reduces postprandial glycemic excursions in IDDM. Diabetes 44:626-630, 1995
116. Creutzfeld WO, Kleine N, Willms B, Orskov C, Holst JJ, Nauck MA: Glucagonostatic actions and reduction of fasting hyperglycemia by exogenous glucagon-like peptide 1(7-36) amide in type 1 diabetic patients. Diabetes Care 19:580-586, 1996
117. Byrne MM, Gliem K, Wank U, Arnold R, Katschinski M, Polonsky KS, Goke B: Glucagon-like peptide 1 improves the ability of the β-cell to sense and respond to glucose in subjects with impaired glucose tolerance. Diabetes 47:1259-1265, 1998
118. Ritzel R, Schulte M, Porksen N, Nauck MS, Holst JJ, Juhl C, Marz W, Schmitz O, Schmiegel WH, Nauck MA: Glucagon-like peptide 1 increases secretory burst mass of pulsatile insulin secretion in patients with type 2 diabetes and impaired glucose tolerance. Diabetes 50:776-784, 2001
119. Kjems LL, Holst JJ, Volund 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
120. D'Alessio DA, Kahn SE, Leusner CR, Ensinck JW: Glucagon-like peptide 1 enhances glucose tolerance both by stimulation of insulin release and by increasing insulin-independent glucose disposal. J Clin Invest 93:2263-2266, 1994
121. D'Alessio DA, Prigeon RL, Ensinck JW: Enteral enhancement of glucose disposition by both insulin-dependent and insulin-independent processes: a physiological role of glucagon-like peptide 1. Diabetes 44:1433-1437, 1995
122. Toft-Nielson M, Madsbad S, Holst JJ: The effect of glucagon-like peptide 1 (GLP-1) on glucose elimination in healthy subjects depends on the pancreatic glucoregulatory hormones. Diabetes 45:552-556, 1996
123. Ryan AS, Egan JM, Habener JF, Elahi D: Insulinotropic hormone glucagon-like peptide-1-(7-37) appears not to augment insulin-mediated glucose uptake in young men during euglycemia. J Clin Endocrinol Metab 83:2399-2404, 1998
124. Vella A, Shah P, Basu R, Basu A, Holst JJ, Rizza RA: Effect of glucagon-like peptide 1(7-36) amide on glucose effectiveness and insulin action in people with type 2 diabetes. Diabetes 49:611-617, 2000
125. 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
126. Nauck MA, Sauerwald A, Ritzel R, Holst JJ, Schmiegel W: Influence of glucagon-like peptide 1 on fasting glycemia in type 2 diabetic patients treated with insulin after sulfonylurea secondary failure. Diabetes Care 21:1925-1931, 1998
127. Gutniak MK, Juntti-Berggren L, Hellstrom PM, Guenifi A, Holst JJ, Efendic S: Glucagon-like peptide I enhances the insulinotropic effect of glibenclamide in NIDDM patients and in the perfused rat pancreas. Diabetes Care 19:857-863, 1996
128. Zander M, Taskiran M, Toft-Nielsen MB, Madsbad S, Holst JJ: Additive glucose-lowering effects of glucagon-like peptide-1 and metformin in type 2 diabetes. Diabetes Care 24:720-725, 2001
129. Miholic J, Orskov 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
130. Edwards CM, Todd JF, Ghatei MA, Bloom SR: Subcutaneous glucagon-like peptide-1 (7-36) amide is insulinotropic and can cause hypoglycaemia in fasted healthy subjects. Clin Sci (Colch) 95:719-724, 1998
131. 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. J Clin Endocrinol Metab 87:1239-1246, 2002
132. 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
133. 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. Am J Physiol 276:R1541-R1544, 1999
134. Toft-Nielsen MB, Madsbad S, Holst JJ: Continuous subcutaneous infusion of glucagon-like peptide 1 lowers plasma glucose and reduces appetite in type 2 diabetic patients. Diabetes Care 22:1137-1143, 1999
135. Naslund E, Barkeling B, King N, Gutniak M, Blundell JE, Holst JJ, Rossner S, Hellstrom PM: Energy intake and appetite are suppressed by glucagon-like peptide-1 (GLP-1) in obese men. Int J Obes Relat Metab Disord 23:304-311, 1999
136. Flint A, Raben A, Ersboll AK, Holst JJ, Astrup A: The effect of physiological levels of glucagon-like peptide-1 on appetite, gastric emptying, energy and substrate metabolism in obesity. Int J Obes Relat Metab Disord 25:781-792, 2001
137. Verdich C, Flint A, Gutzwiller JP, Naslund E, Beglinger C, Hellstrom PM, Long SJ, Morgan LM, Holst JJ, Astrup A: A meta-analysis of the effect of glucagon-like peptide-1 (7-36) amide on ad libitum energy intake in humans. J Clin Endocrinol Metab 86:4382-4389, 2001
138. Nauck MA, Wollschlager D, Werner J, Holst JJ, Orskov C, Creutzfeldt W, Willms B: Effects of subcutaneous glucagon-like peptide 1 (GLP-1[7-36 amide]) in patients with NIDDM. Diabetologia 39:1546-1553, 1996
139. Juntti-Berggren L, Pigon J, Karpe F, Hamsten A, Gutniak M, Vignati L, Efendic S: The antidiabetogenic effect of GLP-1 is maintained during a 7-day treatment period and improves diabetic dyslipoproteinemia in NIDDM patients. Diabetes Care 19:1200-1206, 1996
140. Gutniak MK, Linde B, Holst JJ, Efendic S: Subcutaneous injection of the incretin hormone glucagon-like peptide 1 abolishes postprandial glycemia in NIDDM. Diabetes Care 17:1039-1044, 1994
141. Ritzel R, Orskov C, Holst JJ, Nauck MA: Pharmacokinetic, insulinotropic, and glucagonostatic properties of GLP-1 [7-36 amide] after subcutaneous injection in healthy volunteers: dose-response relationships. Diabetologia 38:720-725, 1995
142. Larsen J, Hylleberg B, Ng K, Damsbo P: Glucagon-like peptide-1 infusion must be maintained for 24 h/day to obtain acceptable glycemia in type 2 diabetic patients who are poorly controlled on sulphonylurea treatment. Diabetes Care 24:1416-1421, 2001
143. Rachman J, Barrow BA, Levy JC, Turner RC: Near normalization of diurnal glucose concentrations by continuous administration of glucagon-like peptide 1 (GLP-1) in subjects with NIDDM. Diabetologia 40:205-211, 1997
144. Todd JF, Wilding JP, Edwards CM, Ghatei MA, Bloom SR: Glucagon-like peptide-1 (GLP-1): a trial of treatment in non-insulin-dependent diabetes mellitus. Eur J Clin Invest 27:533-536, 1997
145. 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 80:952-957, 1995
146. Eng J, Kleinman WA, Singh L, Singh G, Raufman JP: Isolation and characterization of exendin 4, an exendin 3 analogue from Heloderma suspectum venom. J Biol Chem 267:7402-7405, 1992
147. Chen YE, Drucker DJ: Tissue-specific expression of unique mRNAs that encode proglucagon-derived peptides or exendin 4 in the lizard. J Biol Chem 272: 4108-4115, 1997
148. Edwards CM, Stanley SA, Davis R, Brynes AE, Frost GS, Seal LJ, Ghatei MA, Bloom SR: Exendin-4 reduces fasting and postprandial glucose and decreases energy intake in healthy volunteers. Am J Physiol 281:E155-E161, 2001
149. Egan JM, Clocquet AR, Elahi D: The insulinotropic effect of acute exendin-4 administered to humans: comparison of nondiabetic state to type 2 diabetes. J Clin Endocrinol Metab 87:1282-1290, 2002
150. Egan JM, Meneilly GS, Elahi D: Effects of one month bolus subcutaneous administration of exendin-4 in type 2 diabetes. Am J Physiol Endocrinol Metab 34:E1072-E1079, 2003
151. Nielsen LL, Baron AD: Pharmacology of exenatide (synthetic exendin-4) for the treatment of type 2 diabetes. Curr Opin Investig Drugs 4:401-405, 2003
152. Fineman MS, Bicsak TA, Shen LZ, Taylor K, Gaines E, Varns A, Kim DW, Baron AD: Effect on glycemic control of synthetic exendin-4 (AC2993) additive to existing metformin and/or sulfonylurea treatment in patients with type 2 diabetes. Diabetes Care 26:2370-2377, 2003
153. Agerso H, Jensen LB, Elbrond B, Rolan P, Zdravkovic M: The pharmacokinetics, pharmacodynamics, safety and tolerability of NN2211, a new long-acting GLP-1 derivative, in healthy men. Diabetologia 45:195-202, 2002
154. Juhl CB, Hollingdal M, Sturis J, Jakobsen G, Agerso H, Veldhuis J, Porksen N, Schmitz O: Bedtime administration of NN2211, a long-acting GLP-1 derivative, substantially reduces fasting and postprandial glycemia in type 2 diabetes. Diabetes 51:424-429, 2002
155. Drucker DJ: Therapeutic potential of dipeptidyl peptidase IV inhibitors for the treatment of type 2 diabetes. Expert Opin Investig Drugs 12:87-100, 2003
156. Holst JJ, Deacon CF: Inhibition of the activity of dipeptidyl-peptidase IV as a treatment for type 2 diabetes. Diabetes 47:1663-1670, 1998
157. Durinx C, Lambeir AM, Bosmans E, Falmagne JB, Berghmans R, Haemers A, Scharpe S, De Meester I: Molecular characterization of dipeptidyl peptidase activity in serum: soluble CD26/dipeptidyl peptidase IV is responsible for the release of X-Pro dipeptides. Eur J Biochem 267:5608-5613, 2000
158. Marguet D, Baggio L, Kobayashi T, Bernard AM, Pierres M, Nielsen PF, Ribel U, Watanabe T, Drucker DJ, Wagtmann N: Enhanced insulin secretion and improved glucose tolerance in mice lacking CD26. Proc Natl Acad Sci U S A 97: 6874-6879, 2000
159. Nagakura T, Yasuda N, Yamazaki K, Ikuta H, Yoshikawa S, Asano O, Tanaka I: Improved glucose tolerance via enhanced glucose-dependent insulin secretion in dipeptidyl peptidase IV-deficient Fischer rats. Biochem Biophys Res Commun 284:501-506, 2001
160. Conarello SL, Li Z, Ronan J, Roy RS, Zhu L, Jiang G, Liu F, Woods J, Zycband E, Moller DE, Thornberry NA, Zhang BB: Mice lacking dipeptidyl peptidase IV are protected against obesity and insulin resistance. Proc Natl Acad Sci U S A 100: 6825-6830, 2003
161. Ahren B, Holst JJ, Martensson H, Balkan B: Improved glucose tolerance and insulin secretion by inhibition of dipeptidyl peptidase IV in mice. Eur J Pharmacol 404:239-245, 2000
162. Balkan B, Kwasnik L, Miserendino R, Holst JJ, Li X: Inhibition of dipeptidyl peptidase IV with NVP-DPP728 increases plasma GLP-1 (7-36 amide) concentrations and improves oral glucose tolerance in obese Zucker rats. Diabetologia 42:1324-1331, 1999
163. Sudre B, Broqua P, White RB, Ashworth D, Evans DM, Haigh R, Junien JL, Aubert ML: Chronic inhibition of circulating dipeptidyl peptidase IV by FE 999011 delays the occurrence of diabetes in male Zucker diabetic fatty rats. Diabetes 51: 1461-1469, 2002
164. Pospisilik JA, Stafford SG, Demuth HU, Brownsey R, Parkhouse W, Finegood DT, McIntosh CH, Pederson RA: Long-term treatment with the dipeptidyl peptidase IV inhibitor P32/98 causes sustained improvements in glucose tolerance, insulin sensitivity, hyperinsulinemia, and β-cell glucose responsiveness in VDF (fa/fa) Zucker rats. Diabetes 51: 943-950, 2002
165. Pospisilik JA, Stafford SG, Demuth HU, McIntosh CH, Pederson RA: Long-term treatment with dipeptidyl peptidase IV inhibitor improves hepatic and peripheral insulin sensitivity in the VDF Zucker rat: a euglycemic-hyperinsulinemic clamp study. Diabetes 51:2677-2683, 2002
166. Pospisilik JA, Martin J, Doty T, Ehses JA, Pamir N, Lynn FC, Piteau S, Demuth HU, McIntosh CH, Pederson RA: Dipeptidyl peptidase IV inhibitor treatment stimulates β-cell survival and islet neogenesis in streptozotocin-induced diabetic rats. Diabetes 52:741-750, 2003
167. Hoffmann T, Glund K, McIntosh CHS, Pederson RA, Hanefeld M, Rosenkranz B, Demuth H-U: DPPIV inhibition as treatment of type II diabetes. In Cell-Surface Aminopeptidases: Basic and Clinical Aspects. Mitzutani S, Turner AJ, Ino K, Nomura S, Eds. Tokyo, Elsevier Science, 2001, p. 381-387
168. Ahren B, Simonsson E, Larsson H, Landin-Olsson M, Torgeirsson H, Jansson PA, Sandqvist M, Bavenholm P, Efendic S, Eriksson JW, Dickinson S, Holmes D: Inhibition of dipeptidyl peptidase IV improves metabolic control over a 4-week study period in type 2 diabetes. Diabetes Care 25:869-875, 2002
169. Mentlein R: Dipeptidyl-peptidase IV (CD26): role in the inactivation of regulatory peptides. Regul Pept 85:9-24, 1999
170. Gorrell MD, Gysbers V, McCaughan GW: CD26: a multifunctional integral membrane and secreted protein of activated lymphocytes. Scand J Immunol 54: 249-264, 2001
171. Yan S, Marguet D, Dobers J, Reutter W, Fan H: Deficiency of CD26 results in a change of cytokine and immunoglobulin secretion after stimulation by pokeweed mitogen. Eur J Immunol 33:1519-1527, 2003
172. Casadevall N, Nataf J, Viron B, Kolta A, Kiladjian JJ, Martin-Dupont P, Michaud P, Papo T, Ugo V, Teyssandier I, Varet B, Mayeux P: Pure red-cell aplasia and antierythropoietin antibodies in patients treated with recombinant erythropoietin. N Engl J Med 346:469-475, 2002