Role of GLP-1 induced glucagon suppression in type 2 diabetes mellitus

Danish Medical Bulletin

Volumn 57, Issue 9, 2010, Pages

  Hare, Kristine Juul ^a  

^a UNIVERSITY OF COPENHAGEN   (Denmark)

Author keywords

[No Author keywords available]

Indexed keywords

EXENDIN 4; GLUCAGON; GLUCAGON LIKE PEPTIDE 1; GLUCOSE; INSULIN; LIRAGLUTIDE; PANCREAS HORMONE; SITAGLIPTIN; SOMATOSTATIN; VILDAGLIPTIN;

ARTICLE; CLINICAL ARTICLE; CONTROLLED STUDY; FEMALE; GLUCAGON RELEASE; HUMAN; MALE; NON INSULIN DEPENDENT DIABETES MELLITUS; BLOOD; DOSE RESPONSE; GLUCOSE BLOOD LEVEL; GLUCOSE TOLERANCE TEST; INSULIN DEPENDENT DIABETES MELLITUS; METABOLISM; PATHOPHYSIOLOGY; PHYSIOLOGY; SECRETION;

BLOOD GLUCOSE; DIABETES MELLITUS, TYPE 1; DIABETES MELLITUS, TYPE 2; DOSE-RESPONSE RELATIONSHIP, DRUG; FEMALE; GLUCAGON; GLUCAGON-LIKE PEPTIDE 1; GLUCOSE TOLERANCE TEST; HUMANS; INSULIN; MALE;

EID: 77957674132     PISSN: 16039629     EISSN: 16039629     Source Type: Journal    
DOI: None     Document Type: Article

References (197)

1. Nauck, M, Stockmann, F, Ebert, R, Creutzfeldt, W. Reduced incretin effect in type 2 (non-insulin-dependent) diabetes. Diabetologia 29.46-52, 1986
2. Faerch, K, Borch-Johnsen, K, Holst, JJ, Vaag, A. Pathophysiology and aetiology of impaired fasting glycaemia and impaired glucose tolerance. does it matter for prevention and treatment of type 2 diabetes? Diabetologia 52.1714-1723, 2009
3. Bergman, RN. Lilly lecture 1989. Toward physiological understanding of glucose tolerance. Minimal-model approach. Diabetes 38.1512-1527, 1989
4. Kahn, SE. The relative contributions of insulin resistance and beta-cell dysfunction to the pathophysiology of Type 2 diabetes. Diabetologia 46.3-19, 2003
5. Larsson, H, Ahren, B. Failure to adequately adapt reduced insulin sensitivity with increased insulin secretion in women with impaired glucose tolerance. Diabetologia 39.1099-1107, 1996
6. Larsson, H, Ahren, B. Islet dysfunction in obese women with impaired glucose tolerance. Metabolism 45.502-509, 1996
7. Larsson, H, Ahren, B. Insulin resistant subjects lack islet adaptation to short-term dexamethasone-induced reduction in insulin sensitivity. Diabetologia 42.936-943, 1999
8. Turner, RC, Cull, CA, Stratton, IM, Manley, SE, Kohner, EM, Matthews, DR, Neil, HAW, Levy, JC, Holman, RR. Uk rospective Diabetes Study 16 - Overview of 6 Years Therapy of Type-Ii Diabetes - A Progressive Disease. Diabetes 44.1249-1258, 1995
9. Ahren, B, Larsson, H. Impaired glucose tolerance (IGT) is associated with reduced insulin-induced suppression of glucagon concentrations. Diabetologia 44.1998-2003, 2001
10. 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
11. Shah, P, Basu, A, Basu, R, Rizza, R. Impact of lack of suppression of glucagon on glucose tolerance in humans. Am J Physiol 277.E283-E290, 1999
12. 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
13. Orskov, C, Holst, 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
14. Knop, FK, Vilsboll, T, Madsbad, S, Holst, JJ, Krarup, T. Inappropriate suppression of glucagon during OGTT but not during isoglycaemic i.v. glucose infusion contributes to the reduced incretin effect in type 2 diabetes mellitus. Diabetologia 50.797-805, 2007
15. Knop, FK, Vilsboll, T, Hojberg, PV, Larsen, S, Madsbad, S, Volund, A, Holst, JJ, Krarup, T. Reduced incretin effect in type 2 diabetes. cause or consequence of the diabetic state? Diabetes 56.1951-1959, 2007
16. Knop, FK, Aaboe, K, Vilsboll, T, Madsbad, S, Holst, JJ, Krarup, T. Redcuced incretin effect in obese subjects with normal glucose tolerance as compared to lean control subjects. Diabetes 57.A410, 2008
17. Bell, GI, Santerre, RF, Mullenbach, GT. Hamster preproglucagon contains the sequence of glucagon and two related peptides. Nature 302.716-718, 1983
18. Holst, JJ, Bersani, M, Johnsen, AH, Kofod, H, Hartmann, B, Orskov, C. Proglucagon processing in porcine and human pancreas. J Biol Chem 269.18827-18833, 1994
19. Novak, U, Wilks, A, Buell, G, McEwen, S. Identical mRNA for preproglucagon in pancreas and gut. Eur J Biochem 164.553-558, 1987
20. Larsen, PJ, Tang-Christensen, M, Holst, JJ, Orskov, C. Distribution of Glucagon-Like peptide-1 and other preproglucagon-derived peptides in the rat hypothalamus and brainstem. Neuroscience 77.257-270, 1997
21. 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. J Biol Chem 261.11880-11889, 1986
22. Orskov, C, Holst, JJ, Poulsen, SS, Kirkegaard, P. Pancreatic and intestinal processing of proglucagon in man. Diabetologia 30.874-881, 1987
23. Buhl, T, Thim, L, Kofod, H, Orskov, C, Harling, H, Holst, JJ. Naturally occurring products of proglucagon 111-160 in the porcine and human small intestine. J Biol Chem 263.8621-8624, 1988
24. Orskov, 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
25. Orskov, 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
26. Thim, L, Moody, AJ. The primary structure of porcine glicentin (proglucagon). Regul Pept 2.139-150, 1981
27. Thulesen, J. Glucagon-Like peptide 2 (GLP-2), an intestinotrophic mediator. Curr Protein Pept Sci 5.51-65, 2004
28. Cheeseman, CI. Upregulation of SGLT-1 transport activity in rat jejunum induced by GLP-2 infusion in vivo. Am J Physiol 273.R1965-R1971, 1997
29. Jeppesen, PB, Hartmann, B, Thulesen, J, Graff, J, Lohmann, J, Hansen, BS, Tofteng, F, Poulsen, SS, Madsen, JL, Holst, JJ, Mortensen, PB. Glucagon-Like peptide 2 improves nutrient absorption and nutritional status in short-bowel patients with no colon. Gastroenterology 120.806-815, 2001
30. Martin, GR, Beck, PL, Sigalet, DL. Gut hormones, and short bowel syndrome. the enigmatic role of glucagonlike peptide-2 in the regulation of intestinal adaptation. World J Gastroenterol 12.4117-4129, 2006
31. Hare, KJ, Hartmann, B, Kissow, H, Holst, JJ, Poulsen, SS. The intestinotrophic peptide, glp-2, counteracts intestinal atrophy in mice induced by the epidermal growth factor receptor inhibitor, gefitinib. Clin Cancer Res 13.5170-5175, 2007
32. Henriksen, DB, Alexandersen, P, Bjarnason, NH, Vilsboll, T, Hartmann, B, Henriksen, EE, Byrjalsen, I, Krarup, T, Holst, JJ, Christiansen, C. Role of gastrointestinal hormones in postprandial reduction of bone resorption. J Bone Miner Res 18.2180-2189, 2003
33. Henriksen, DB, Alexandersen, P, Hartmann, B, Adrian, CL, Byrjalsen, I, Bone, HG, Holst, JJ, Christiansen, C. Disassociation of bone resorption and formation by GLP-2. a 14-day study in healthy postmenopausal women. Bone 40.723-729, 2007
34. Wynne, K, Park, AJ, Small, CJ, Patterson, M, Ellis, SM, Murphy, KG, Wren, AM, Frost, GS, Meeran, K, Ghatei, MA, Bloom, SR. Subcutaneous oxyntomodulin reduces body weight in overweight and obese subjects. a doubleblind, randomized, controlled trial. Diabetes 54.2390-2395, 2005
35. Wynne, K, Park, AJ, Small, CJ, Meeran, K, Ghatei, MA, Frost, GS, Bloom, SR. Oxyntomodulin increases energy expenditure in addition to decreasing energy intake in overweight and obese humans. a randomised controlled trial. Int J Obes (Lond) 30.1729-1736, 2006
36. Alford, FP, Bloom, SR, Nabarro, JD, Hall, R, Besser, GM, Coy, DH, Kastin, AJ, Schally, AV. Glucagon control of fasting glucose in man. Lancet 2.974-977, 1974
37. Cherrington, AD, Chiasson, JL, Liljenquist, JE, Lacy, WW, Park, CR. Control of hepatic glucose output by glucagons and insulin in the intact dog. Biochem Soc Symp31-45, 1978
38. Gromada, J, Franklin, I, Wollheim, CB. Alpha-cells of the endocrine pancreas. 35 years of research but the enigma remains. Endocr Rev 28.84-116, 2007
39. Jelinek, LJ, Lok, S, Rosenberg, GB, Smith, RA, Grant, FJ, Biggs, S, Bensch, PA, Kuijper, JL, Sheppard, PO, Sprecher, CA,Expression cloning and signaling properties of the rat glucagon receptor. Science 259.1614-1616, 1993
40. Jiang, G, Zhang, BB. Glucagon and regulation of glucose metabolism. Am J Physiol Endocrinol Metab 284.E671-E678, 2003
41. Consoli, A, Nurjhan, N, Capani, F, Gerich, J. Predominant role of gluconeogenesis in increased hepatic glucose production in NIDDM. Diabetes 38.550-557, 1989
42. Gastaldelli, A, Miyazaki, Y, Pettiti, M, Buzzigoli, E, Mahankali, S, Ferrannini, E, DeFronzo, RA. Separate contribution of diabetes, total fat mass, and fat topography to glucose production, gluconeogenesis, and glycogenolysis. J Clin Endocrinol Metab 89.3914-3921, 2004
43. Lefebvre, PJ. The intriguing diversity of the glucagons gene products. Curr Diab Rep 2.201-202, 2002
44. Ali, S, Drucker, DJ. Benefits and limitations of reducing glucagon action for the treatment of type 2 diabetes. Am J Physiol Endocrinol Metab 296.E415-E421, 2009
45. Hansen, LH, Abrahamsen, N, Nishimura, E. Glucagon receptor mRNA distribution in rat tissues. Peptides 16.1163-1166, 1995
46. Kieffer, TJ, Heller, RS, Unson, CG, Weir, GC, Habener, JF. Distribution of glucagon receptors on hormone-specific endocrine cells of rat pancreatic islets. Endocrinology 137.5119-5125, 1996
47. Moens, K, Heimberg, H, Flamez, D, Huypens, P, Quartier, E, Ling, Z, Pipeleers, D, Gremlich, S, Thorens, B, Schuit, F. Expression and functional activity of glucagon, glucagonlike peptide I, and glucose-dependent insulinotropic peptide receptors in rat pancreatic islet cells. Diabetes 45.257-261, 1996
48. Moens, K, Flamez, D, Van, SC, Ling, Z, Pipeleers, D, Schuit, F. Dual glucagon recognition by pancreatic betacells via glucagon and Glucagon-Like peptide 1 receptors. Diabetes 47.66-72, 1998
49. Ma, X, Zhang, Y, Gromada, J, Sewing, S, Berggren, PO, Buschard, K, Salehi, A, Vikman, J, Rorsman, P, Eliasson, L. Glucagon stimulates exocytosis in mouse and rat pancreatic alpha-cells by binding to glucagon receptors. Mol Endocrinol 19.198-212, 2005
50. Hope, KM, Tran, PO, Zhou, H, Oseid, E, Leroy, E, Robertson, RP. Regulation of alpha-cell function by the betacell in isolated human and rat islets deprived of glucose. the switch-off hypothesis. Diabetes 53.1488-1495, 2004
51. Samols, E, Stagner, JI, Ewart, RB, Marks, V. The order of islet microvascular cellular perfusion is B----A----D in the perfused rat pancreas. J Clin Invest 82.350-353, 1988
52. Raju, B, Cryer, PE. Loss of the decrement in intraislet insulin plausibly explains loss of the glucagon response to hypoglycemia in insulin-deficient diabetes. documentation of the intraislet insulin hypothesis in humans. Diabetes 54.757-764, 2005
53. Hare, KJ, Knop, FK, Asmar, M, Larsen, S, Madsbad, S, Holst, JJ, Vilsboll, T. Preserved Inhibitory Effect of Glucagon- Like Peptide-1 (GLP-1) on Glucagon Secretion in Type 2 Diabetes Mellitus. Diabetes 58.A372, 2009
54. Asmar, M, Knop, FK, Bache, M, Vilsboll, T, Madsbad, S, Holst, JJ. Human amylin, pramlintide and GLP-1. Influence on gastric emptying, appetite and food intake in humans. Diabetes 57.A406-A407, 2008
55. Ishihara, H, Maechler, P, Gjinovci, A, Herrera, PL, Wollheim, CB. Islet beta-cell secretion determines glucagons release from neighbouring alpha-cells. Nat Cell Biol 5.330-335, 2003
56. Luft, R, Efendic, S, Hokfelt, T. Somatostatin--both hormone and neurotransmitter? Diabetologia 14.1-13, 1978
57. Sakurai, H, Dobbs, R, Unger, RH. Somatostatin-induced changes in insulin and glucagon secretion in normal and diabetic dogs. J Clin Invest 54.1395-1402, 1974
58. Ludvigsen, E, Olsson, R, Stridsberg, M, Janson, ET, Sandler, S. Expression and distribution of somatostatin receptor subtypes in the pancreatic islets of mice and rats. J Histochem Cytochem 52.391-400, 2004
59. Portela-Gomes, GM, Stridsberg, M, Grimelius, L, Oberg, K, Janson, ET. Expression of the five different somatostatin receptor subtypes in endocrine cells of the pancreas. Appl Immunohistochem Mol Morphol 8.126-132, 2000
60. de, HJ, 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 51.2263-2270, 2008
61. Rossowski, WJ, Coy, DH. Specific inhibition of rat pancreatic insulin or glucagon release by receptor-selective somatostatin analogs. Biochem Biophys Res Commun 205.341-346, 1994
62. Charollais, A, Gjinovci, A, Huarte, J, Bauquis, J, Nadal, A, Martin, F, Andreu, E, Sanchez-Andres, JV, Calabrese, A, Bosco, D, Soria, B, Wollheim, CB, Herrera, PL, Meda, P. Junctional communication of pancreatic beta cells contributes to the control of insulin secretion and glucose tolerance. J Clin Invest 106.235-243, 2000
63. Kleinman, R, Gingerich, R, Ohning, G, Wong, H, Olthoff, K, Walsh, J, Brunicardi, FC. The influence of somatostatin on glucagon and pancreatic polypeptide secretion in the isolated perfused human pancreas. Int J Pancreatol 18.51-57, 1995
64. Brissova, M, Fowler, MJ, Nicholson, WE, Chu, A, Hirshberg, B, Harlan, DM, Powers, AC. Assessment of human pancreatic islet architecture and composition by laser scanning confocal microscopy. J Histochem Cytochem 53.1087-1097, 2005
65. Cabrera, O, Berman, DM, Kenyon, NS, Ricordi, C, Berggren, PO, Caicedo, A. The unique cytoarchitecture of human pancreatic islets has implications for islet cell function. Proc Natl Acad Sci U S A 103.2334-2339, 2006
66. Kharouta, M, Miller, K, Kim, A, Wojcik, P, Kilimnik, G, Dey, A, Steiner, DF, Hara, M. No mantle formation in rodent islets -- the prototype of islet revisited. Diabetes Res Clin Pract 85.252-257, 2009
67. Brelje, TC, Scharp, DW, Sorenson, RL. Three-dimensional imaging of intact isolated islets of Langerhans with confocal microscopy. Diabetes 38.808-814, 1989
68. Weir, GC, Bonner-Weir, S. Islets of Langerhans. the puzzle of intraislet interactions and their relevance to diabetes. J Clin Invest 85.983-987, 1990
69. Samols, E, Bonner-Weir, S, Weir, GC. Intra-islet insulinglucagon-somatostatin relationships. Clin Endocrinol Metab 15.33-58, 1986
70. Creutzfeldt, WO, Kleine, N, Willms, B, Orskov, C, Holst, JJ, Nauck, MA. Glucagonostatic actions and reduction of fasting hyperglycemia by exogenous Glucagon-Like peptide I(7-36) amide in type I diabetic patients. Diabetes Care 19.580-586, 1996
71. Pederson, RA, Brown, JC. Interaction of gastric inhibitory polypeptide, glucose, and arginine on insulin and glucagons secretion from the perfused rat pancreas. Endocrinology 103.610-615, 1978
72. Creutzfeldt, W, Nauck, M. Gut hormones and diabetes mellitus. Diabetes Metab Rev 8.149-177, 1992
73. 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
74. Christensen, M, Knop, FK, Vilsboll, T, Aaboe, K, Holst, JJ, Krarup, T, Madsbad, S. Glucagon-Like peptide-2, but Not Glucose-Dependent Insulinotropic Polypeptide, Stimulates Glucagon Release in Patients with Type 1 Diabetes Mellitus. Diabetes 58.A368, 2009
75. Dupre, J, Caussignac, Y, McDonald, TJ, Van, VS. Stimulation of glucagon secretion by gastric inhibitory polypeptide in patients with hepatic cirrhosis and hyperglucagonemia. J Clin Endocrinol Metab 72.125-129, 1991
76. Meier, JJ, Gallwitz, B, Siepmann, N, Holst, JJ, Deacon, CF, Schmidt, WE, Nauck, MA. Gastric inhibitory polypeptide (GIP) dose-dependently stimulates glucagon secretion in healthy human subjects at euglycaemia. Diabetologia 46.798-801, 2003
77. 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 27.450-456, 2003
78. Meier, JJ, Nauck, MA, Pott, A, Heinze, K, Goetze, O, Bulut, K, Schmidt, WE, Gallwitz, B, Holst, JJ. Glucagon-Like peptide 2 stimulates glucagon secretion, enhances lipid absorption, and inhibits gastric acid secretion in humans. Gastroenterology 130.44-54, 2006
79. de, HJ, Pedersen, J, Orskov, C, Holst, JJ. The alpha cell expresses Glucagon-Like peptide-2 receptors and glucagon- like peptide-2 stimulates glucagon secretion from the rat pancreas. Diabetologia 50.2135-2142, 2007
80. Schmidt, WE, Siegel, EG, Creutzfeldt, W. Glucagon-Like peptide-1 but not Glucagon-Like peptide-2 stimulates insulin release from isolated rat pancreatic islets. Diabetologia 28.704-707, 1985
81. Unger, RH, Orci, L. Glucagon and the A cell. physiology and pathophysiology (second of two parts). N Engl J Med 304.1575-1580, 1981
82. Unger, RH, Orci, L. Glucagon and the A cell. physiology and pathophysiology (first two parts). N Engl J Med 304.1518-1524, 1981
83. Nauck, MA, Meier, JJ, Wolfersdorff, AV, Tillil, H, Creutzfeldt, W, Kobberling, J. A 25-year follow-up study of glucose tolerance in first-degree relatives of type 2 diabetic patients. association of impaired or diabeticglucose tolerance with other components of the metabolic syndrome. Acta Diabetol 40.163-172, 2003
84. Meier, JJ, Deacon, CF, Schmidt, WE, Holst, JJ, Nauck, MA. Suppression of glucagon secretion is lower after oral glucose administration than during intravenous glucose administration in human subjects. Diabetologia 50.806-813, 2007
85. Hojberg, PV, Vilsboll, T, Rabol, R, Knop, FK, Bache, M, Krarup, T, Holst, JJ, Madsbad, S. Four weeks of earnormalisation of blood glucose improves the insulin response to Glucagon-Like peptide-1 and glucosedependent insulinotropic polypeptide in patients with type 2 diabetes. Diabetologia 52.199-207, 2009
86. Baron, AD, Schaeffer, L, Shragg, P, Kolterman, OG. Role of hyperglucagonemia in maintenance of increased rates of hepatic glucose output in type II diabetics. Diabetes 36.274-283, 1987
87. Basu, R, Schwenk, WF, Rizza, RA. Both fasting glucose production and disappearance are abnormal in people with mild and severe type 2 diabetes. Am J Physiol Endocrinol Metab 287.E55-E62, 2004
88. Hojberg, PV, Zander, M, Vilsboll, T, Knop, FK, Krarup, T, Volund, A, Holst, JJ, Madsbad, S. Near normalisation of blood glucose improves the potentiating effect of GLP-1 on glucose-induced insulin secretion in patients with type 2 diabetes. Diabetologia 51.632-640, 2008
89. Raskin, P, Aydin, I, Yamamoto, T, Unger, RH. Abnormal alpha cell function in human diabetes. the response to oral protein. Am J Med 64.988-997, 1978
90. 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
91. Ohneda, A, Watanabe, K, Horigome, K, Sakai, T, Kai, Y, Oikawa, S. Abnormal response of pancreatic glucagon to glycemic changes in diabetes mellitus. J Clin Endocrinol Metab 46.504-510, 1978
92. Unger, RH, guilar-Parada, E, Muller, WA, Eisentraut, AM. Studies of pancreatic alpha cell function in normal and diabetic subjects. J Clin Invest 49.837-848, 1970
93. Woerle, HJ, Szoke, E, Meyer, C, Dostou, JM, Wittlin, SD, Gosmanov, NR, Welle, SL, Gerich, JE. Mechanisms for abnormal postprandial glucose metabolism in type 2 diabetes. Am J Physiol Endocrinol Metab 290.E67-E77, 2006
94. Gerich, JE, Charles, MA, Grodsky, GM. Regulation of pancreatic insulin and glucagon secretion. Annu Rev Physiol 38.353-388, 1976
95. Stagner, JI, Samols, E. The vascular order of islet cellular perfusion in the human pancreas. Diabetes 41.93-97, 1992
96. Hamaguchi, T, Fukushima, H, Uehara, M, Wada, S, Shirotani, T, Kishikawa, H, Ichinose, K, Yamaguchi, K, Shichiri, M. Abnormal glucagon response to arginine and its normalization in obese hyperinsulinaemic patients with glucose intolerance. importance of insulin action on pancreatic alpha cells. Diabetologia 34.801-806, 1991
97. Ward, WK, Bolgiano, DC, McKnight, B, Halter, JB, Porte, D, Jr.Diminished B cell secretory capacity in patients with noninsulin-dependent diabetes mellitus. J Clin Invest 74.1318-1328, 1984
98. Segel, SA, Paramore, DS, Cryer, PE. Hypoglycemiaassociated autonomic failure in advanced type 2 diabetes. Diabetes 51.724-733, 2002
99. Cryer, PE. Diverse causes of hypoglycemia-associated autonomic failure in diabetes. N Engl J Med 350.2272-2279, 2004
100. Bolli, GB, De, FP, De, CS, Perriello, G, Ventura, MM, Benedetti, MM, Santeusanio, F, Gerich, JE, Brunetti, P. A reliable and reproducible test for adequate glucose counterregulation in type I diabetes mellitus. Diabetes 33.732-737, 1984
101. Gerich, JE, Langlois, M, Noacco, C, Karam, JH, Forsham, PH. Lack of glucagon response to hypoglycemia in diabetes. evidence for an intrinsic pancreatic alpha cell defect. Science 182.171-173, 1973
102. Ahren, B, Holst, JJ. The cephalic insulin response to meal ingestion in humans is dependent on both cholinergic and noncholinergic mechanisms and is important for postprandial glycemia. Diabetes 50.1030-1038, 2001
103. Dube, PE, Brubaker, PL. Nutrient, neural and endocrine control of Glucagon-Like peptide secretion. Horm Metab Res 36.755-760, 2004
104. Eissele, R, Goke, R, Willemer, S, Harthus, HP, Vermeer, H, Arnold, R, Goke, B. Glucagon-Like peptide-1 cells in the gastrointestinal tract and pancreas of rat, pig and man. Eur J Clin Invest 22.283-291, 1992
105. 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 8.1646-1655, 1994
106. Herrmann, C, Goke, R, Richter, G, Fehmann, HC, Arnold, R, Goke, B. Glucagon-Like peptide-1 and glucosedependent insulin-releasing polypeptide plasma levels in response to nutrients. Digestion 56.117-126, 1995
107. Gribble, FM, Williams, L, Simpson, AK, Reimann, F. A novel glucose-sensing mechanism contributing to glucagonlike peptide-1 secretion from the GLUTag cell line. Diabetes 52.1147-1154, 2003
108. Rozengurt, E, Sternini, C. Taste receptor signaling in the mammalian gut. Curr Opin Pharmacol 7.557-562, 2007
109. Tolhurst, G, Reimann, F, Gribble, FM. Nutritional regulation of Glucagon-Like peptide-1 secretion. J Physiol 587.27-32, 2009
110. Reimann, F, Williams, L, da, S, X, Rutter, GA, Gribble, FM. Glutamine potently stimulates Glucagon-Like peptide-1 secretion from GLUTag cells. Diabetologia 47.1592-1601, 2004
111. Abello, J, Ye, F, Bosshard, A, Bernard, C, Cuber, JC, Chayvialle, JA. Stimulation of Glucagon-Like peptide-1 secretion by muscarinic agonist in a murine intestinal endocrine cell line. Endocrinology 134.2011-2017, 1994
112. Balks, HJ, Holst, JJ, von zur, MA, Brabant, G. Rapid oscillations in plasma Glucagon-Like peptide-1 (GLP-1) in humans. cholinergic control of GLP-1 secretion via muscarinic receptors. J Clin Endocrinol Metab 82.786-790, 1997
113. Herrmann-Rinke, C, Voge, A, Hess, M, Goke, B. Regulation of Glucagon-Like peptide-1 secretion from rat ileum by neurotransmitters and peptides. J Endocrinol 147.25-31, 1995
114. Edfalk, S, Steneberg, P, Edlund, H. Gpr40 is expressed in enteroendocrine cells and mediates free fatty acidstimulation of incretin secretion. Diabetes 57.2280-2287, 2008
115. Hirasawa, A, Tsumaya, K, Awaji, T, Katsuma, S, Adachi, T, Yamada, M, Sugimoto, Y, Miyazaki, S, Tsujimoto, G. Free fatty acids regulate gut incretin Glucagon-Like peptide-1 secretion through GPR120. Nat Med 11.90-94, 2005
116. Thomas, C, Gioiello, A, Noriega, L, Strehle, A, Oury, J, Rizzo, G, Macchiarulo, A, Yamamoto, H, Mataki, C, Pruzanski, M, Pellicciari, R, Auwerx, J, Schoonjans, K. TGR5-mediated bile acid sensing controls glucose homeostasis. Cell Metab 10.167-177, 2009
117. Deacon, CF, Nauck, MA, Toft-Nielsen, M, 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
118. Mentlein, R. Dipeptidyl-peptidase IV (CD26)--role in the inactivation of regulatory peptides. Regul Pept 85.9-24, 1999
119. Deacon, CF, Johnsen, AH, Holst, JJ. Degradation of Glucagon-Like peptide-1 by human plasma in vitro yields an Nterminally truncated peptide that is a major endogenous metabolite in vivo. J Clin Endocrinol Metab 80.952-957, 1995
120. Gefel, D, Hendrick, GK, Mojsov, S, Habener, J, Weir, GC. Glucagon-Like peptide-I analogs. effects on insulin secretion and adenosine 3', 5'-monophosphate formation. Endocrinology 126.2164-2168, 1990
121. Deacon, CF, Pridal, L, Klarskov, L, Olesen, M, Holst, JJ. Glucagon-Like peptide 1 undergoes differential tissuespecific metabolism in the anesthetized pig. Am J Physiol 271.E458-E464, 1996
122. 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 140.5356-5363, 1999
123. 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
124. Holz, GG. Epac. A new cAMP-binding protein in support of Glucagon-Like peptide-1 receptor-mediated signal transduction in the pancreatic beta-cell. Diabetes 53.5-13, 2004
125. Ding, WG, Renstrom, E, Rorsman, P, Buschard, K, Gromada, J. Glucagon-Like peptide I and glucose-dependent insulinotropic polypeptide stimulate Ca2+-induced secretion in rat alpha-cells by a protein kinase A-mediated mechanism. Diabetes 46.792-800, 1997
126. 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
127. 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
128. Hvidberg, A, Nielsen, MT, Hilsted, J, Orskov, C, Holst, JJ. Effect of Glucagon-Like peptide-1 (proglucagon 78-107amide) on hepatic glucose production in healthy an. Metabolism 43.104-108, 1994
129. Holst, JJ. On the physiology of GIP and GLP-1. Horm Metab Res 36.747-754, 2004
130. Hare, KJ, Knop, FK, Asmar, M, Madsbad, S, Deacon, CF, Holst, JJ, Vilsboll, T. Preserved Inhibitory Potency of GLP- 1 on Glucagon Secretion in Type 2 Diabetes Mellitus. J Clin Endocrinol Metab 2009
131. Farilla, L, Bulotta, A, Hirshberg, B, Li, CS, Khoury, N, Noushmehr, H, Bertolotto, C, Di, MU, Harlan, DM, Perfetti, R. Glucagon-Like peptide 1 inhibits cell apoptosis and improves glucose responsiveness of freshly isolated human islets. Endocrinology 144.5149-5158, 2003
132. 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
133. 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
134. 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
135. 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
136. Holst, JJ. The physiology of Glucagon-Like peptide 1. Physiol Rev 87.1409-1439, 2007
137. Bullock, BP, Heller, RS, Habener, JF. Tissue distribution of messenger ribonucleic acid encoding the rat glucagonlike peptide-1 receptor. Endocrinology 137.2968-2978, 1996
138. Ban, K, Noyan-Ashraf, MH, Hoefer, J, Bolz, SS, Drucker, DJ, Husain, M. Cardioprotective and vasodilatory actions of Glucagon-Like peptide 1 receptor are mediated through both Glucagon-Like peptide 1 receptor-dependent and -independent pathways. Circulation 117.2340-2350, 2008
139. Sonne, DP, Engstrom, T, Treiman, M. Protective effects of GLP-1 analogues exendin-4 and GLP-1(9-36) amide against ischemia-reperfusion injury in rat heart. Regul Pept 146.243-249, 2008
140. Sokos, GG, Nikolaidis, LA, Mankad, S, Elahi, D, Shannon, RP. Glucagon-Like peptide-1 infusion improves left ventricular ejection fraction and functional status in patients with chronic heart failure. J Card Fail 12.694-699, 2006
141. Sokos, GG, Bolukoglu, H, German, J, Hentosz, T, Magovern, GJ, Jr., Maher, TD, Dean, DA, Bailey, SH, Marrone, G, Benckart, DH, Elahi, D, Shannon, RP. Effect of glucagonlike peptide-1 (GLP-1) on glycemic control and left ventricular function in patients undergoing coronary artery bypass grafting. Am J Cardiol 100.824-829, 2007
142. Nystrom, T, Gutniak, MK, Zhang, Q, Zhang, F, Holst, JJ, Ahren, B, Sjoholm, A. Effects of Glucagon-Like peptide-1 on endothelial function in type 2 diabetes patients with stable coronary artery disease. Am J Physiol Endocrinol Metab 287.E1209-E1215, 2004
143. Klonoff, DC, Buse, JB, Nielsen, LL, Guan, X, Bowlus, CL, Holcombe, JH, Wintle, ME, Maggs, DG. Exenatide effects on diabetes, obesity, cardiovascular risk factors and hepatic biomarkers in patients with type 2 diabetes treated for at least 3 years. Curr Med Res Opin 24.275-286, 2008
144. Vilsboll, T, Zdravkovic, M, Le-Thi, T, Krarup, T, Schmitz, O, Courreges, JP, Verhoeven, R, Buganova, I, Madsbad, S. Liraglutide, a long-acting human Glucagon-Like peptide-1 analog, given as monotherapy significantly improves glycemic control and lowers body weight without risk of hypoglycemia in patients with type 2 diabetes. Diabetes Care 30.1608-1610, 2007
145. Basu, A, Charkoudian, N, Schrage, W, Rizza, RA, Basu, R, Joyner, MJ. Beneficial effects of GLP-1 on endothelial function in humans. dampening by glyburide but not by glimepiride. Am J Physiol Endocrinol Metab 293.E1289- E1295, 2007
146. Muscelli, E, Mari, A, Casolaro, A, Camastra, S, Seghieri, G, Gastaldelli, A, Holst, JJ, Ferrannini, E. Separate impact of obesity and glucose tolerance on the incretin effect in normal subjects and type 2 diabetic patients. Diabetes 57.1340-1348, 2008
147. Vilsboll, T, Kosinski, M, Holst, JJ, Cypryk, K, Knop, F. The reduced incretin effect in diabetes mellitus is completely reversible. Diabetes 57.A411-A412, 2008
148. Hansen, KB, Vilsboll, T, Holst, JJ, Knop, FK. Impaired Incretin Effect Can Be Induced in Healthy Normal Glucose Tolerant Subject. Diabetes 58.A378, 2009
149. Jensen, DH, Aaboe, K, Henriksen, JE, Madsbad, S, Krarup, T. Reduced incretin effect in dexamethasoneinduced insulin resistance and glucose intolerance in diabetic offspring. Diabetologia 52.S227-S228, 2009
150. 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
151. Vaag, AA, Holst, JJ, Volund, A, Beck-Nielsen, HB. Gut incretin hormones in identical twins discordant for noninsulin- 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
152. 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
153. Nauck, MA, Heimesaat, MM, Orskov, C, Holst, JJ, Ebert, R, Creutzfeldt, W. Preserved incretin activity of glucagonlike 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
154. Meier, JJ. The contribution of incretin hormones to the pathogenesis of type 2 diabetes. Best Pract Res Clin ndocrinol Metab 23.433-441, 2009
155. Degn, KB, Brock, B, Juhl, CB, Djurhuus, CB, Grubert, J, Kim, D, Han, J, Taylor, K, Fineman, M, Schmitz, O. Effect of intravenous infusion of exenatide (synthetic exendin-4) on glucose-dependent insulin secretion and counterregulation during hypoglycemia. Diabetes 53.2397-2403, 2004
156. Dunning, BE, Foley, JE, Ahren, B. Alpha cell function in health and disease. influence of Glucagon-Like peptide- 1. Diabetologia 48.1700-1713, 2005
157. Vilsboll, 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
158. 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
159. Kielgast, U, Madsbad, S, Holst, J. Impact of endogenous and exogenous GLP-1 on glucagon secretion in type 1 diabetic patients with and without residual beta -cell function. Diabetologia 52.S58-S59, 2009
160. 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
161. Gutniak, MK, Larsson, H, Sanders, SW, Juneskans, O, Holst, JJ, Ahren, B. GLP-1 tablet in type 2 diabetes in fasting and postprandial conditions. Diabetes Care 20.1874-1879, 1997
162. Meier, JJ, Gallwitz, B, Salmen, S, Goetze, O, Holst, JJ, Schmidt, WE, Nauck, MA. Normalization of glucose concentrations and deceleration of gastric emptying after solid meals during intravenous Glucagon-Like peptide 1 in patients with type 2 diabetes. J Clin Endocrinol Metab 88.2719-2725, 2003
163. Behme, MT, Dupre, J, McDonald, TJ. Glucagon-Like peptide 1 improved glycemic control in type 1 diabetes. BMC Endocr Disord 3.3, 2003
164. Ahren, B, Larsson, H, Holst, JJ. Effects of Glucagon-Like peptide-1 on islet function and insulin sensitivity in noninsulin-dependent diabetes mellitus. J Clin Endocrinol Metab 82.473-478, 1997
165. 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
166. Degn, KB, Juhl, CB, Sturis, J, Jakobsen, G, Brock, B, Chandramouli, V, Rungby, J, Landau, BR, Schmitz, O. One week's treatment with the long-acting Glucagon-Like peptide 1 derivative liraglutide (NN2211) markedly improves 24-h glycemia and alpha- and beta-cell function and reduces endogenous glucose release in patients with type 2 diabetes. Diabetes 53.1187-1194, 2004
167. Ahren, B, Landin-Olsson, M, Jansson, PA, Svensson, M, Holmes, D, Schweizer, A. Inhibition of dipeptidyl peptidase- 4 reduces glycemia, sustains insulin levels, and reduces glucagon levels in type 2 diabetes. J Clin Endocrinol Metab 89.2078-2084, 2004
168. Foley, JE, Ligueros-Saylan, M, He, YL, Holst, JJ, Deacon, CF, Dunning, BE, Leone-Jones, A, Yu, T, Kelley, DE. Effect of vildagliptin on glucagon concentration during meals in patients with type 1 diabetes. Horm Metab Res 40.727-730, 2008
169. Heller, RS, Kieffer, TJ, Habener, JF. Insulinotropic Glucagon-Like peptide I receptor expression in glucagonproducing alpha-cells of the rat endocrine pancreas. Diabetes 46.785-791, 1997
170. Tornehave, D, Kristensen, P, Romer, J, Knudsen, LB, Heller, RS. Expression of the GLP-1 receptor in mouse, rat, and human pancreas. J Histochem Cytochem 56.841-851, 2008
171. Fehmann, HC, Habener, JF. Functional receptors for the insulinotropic hormone Glucagon-Like peptide-I(7-37) on a somatostatin secreting cell line. FEBS Lett 279.335-340, 1991
172. Ahren, B, Lundquist, I. Glucagon immunoreactivity in plasma from normal and dystrophic mice. Diabetologia 22.258-263, 1982
173. Baldissera, FG, Holst, JJ. Glicentin 1-61 probably represents a major fraction of glucagon-related peptides in plasma of anaesthetized uraemic pigs. Diabetologia 29.462-467, 1986
174. Holst, JJ. Evidence that glicentin contains the entire sequence of glucagon. Biochem J 187.337-343, 1980
175. Holst, JJ. Evidence that enteroglucagon (II) is identical with the C-terminal sequence (residues 33-69) of glicentin. Biochem J 207.381-388, 1982
176. Orskov, 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
177. Holst, JJ. Extraction, gel filtration pattern, and receptor binding of porcine gastrointestinal glucagon-like immunoreactivity. Diabetologia 13.159-169, 1977
178. Hare, KJ, Knop, FK, Torang, S, Madsbad, S, Krarup, T, Vilsboll, T, Holst, JJ. Hyperglucagonemia in patients with type 2 diabetes mellitus - Molecular analysis of postprandial glucagon responses. Diabetes 57.A407, 2008
179. Vilsboll, T, Krarup, T, Sonne, J, Madsbad, S, Volund, 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
180. Buse, JB, Rosenstock, J, Sesti, G, Schmidt, WE, Montanya, E, Brett, JH, Zychma, M, Blonde, L. Liraglutide once a day versus exenatide twice a day for type 2 diabetes. a 26-week randomised, parallel-group, multinational, open-label trial (LEAD-6). Lancet 374.39-47, 2009
181. Drucker, DJ, Buse, JB, Taylor, K, Kendall, DM, Trautmann, M, Zhuang, D, Porter, L. Exenatide once weekly versus twice daily for the treatment of type 2 diabetes. a randomised, open-label, non-inferiority study. Lancet 372.1240-1250, 2008
182. Shah, P, Vella, A, Basu, A, Basu, R, Schwenk, WF, Rizza, RA. Lack of suppression of glucagon contributes to postprandial hyperglycemia in subjects with type 2 diabetes mellitus. J Clin Endocrinol Metab 85.4053-4059, 2000
183. 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
184. Holst, JJ, Burcharth, F, Kuhl, C. Pancreatic glucoregulatory hormones in cirrhosis of the liver. portal vein concentrations during intravenous glucose tolerance test and in response to a meal. Diabete Metab 6.117-127, 1980
185. Orskov, L, Holst, JJ, Moller, J, Orskov, C, Moller, N, Alberti, KG, Schmitz, O. GLP-1 does not not acutely affectinsulin ensitivity in healthy man. Diabetologia 39.1227-1232, 1996
186. Greenbaum, CJ, Prigeon, RL, D'Alessio, DA. Impaired betacell function, incretin effect, and glucagon suppression in patients with type 1 diabetes who have normal fasting glucose. Diabetes 51.951-957, 2002
187. Porksen, S, Nielsen, LB, Kaas, A, Kocova, M, Chiarelli, F, Orskov, C, Holst, JJ, Ploug, KB, Hougaard, P, Hansen, L, Mortensen, HB. Meal-stimulated glucagon release is associated with postprandial blood glucose level and does not interfere with glycemic control in children and adolescents with new-onset type 1 diabetes. J Clin Endocrinol Metab 92.2910-2916, 2007
188. King, H, Aubert, RE, Herman, WH. Global burden of diabetes, 1995-2025. prevalence, numerical estimates, and projections. Diabetes Care 21.1414-1431, 1998
189. Vilsboll, T, Holst, JJ, Knop, FK. The spectrum of antidiabetic actions of GLP-1 in patients with diabetes. Best Pract Res Clin Endocrinol Metab 23.453-462, 2009
190. Kodra, JT, Jorgensen, AS, Andersen, B, Behrens, C, Brand, CL, Christensen, IT, Guldbrandt, M, Jeppesen, CB, Knudsen, LB, Madsen, P, Nishimura, E, Sams, C, Sidelmann, UG, Pedersen, RA, Lynn, FC, Lau, J. Novel glucagons receptor antagonists with improved selectivity over the glucose-dependent insulinotropic polypeptide receptor. J Med Chem 51.5387-5396, 2008
191. Madsen, P, Kodra, JT, Behrens, C, Nishimura, E, Jeppesen, CB, Pridal, L, Andersen, B, Knudsen, LB, Valcarce-Aspegren, C, Guldbrandt, M, Christensen, IT, Jorgensen, AS, Ynddal, L, Brand, CL, Bagger, MA, Lau, J. Human glucagon receptor antagonists with thiazole cores. A novel series with superior pharmacokinetic properties. J Med Chem 52.2989-3000, 2009
192. Gilbert, MP, Pratley, RE. Efficacy and safety of incretinbased therapies in patients with type 2 diabetes mellitus. Eur J Intern Med 20 Suppl 2.S309-S318, 2009
193. Mannucci, E, Tesi, F, Bardini, G, Ognibene, A, Petracca, MG, Ciani, S, Pezzatini, A, Brogi, M, Dicembrini, I, Cremasco, F, Messeri, G, Rotella, CM. Effects o f metformin on Glucagon-Like peptide-1 levels in obese patients with and without Type 2 diabetes. Diabetes Nutr Metab 17.336-342, 2004
194. Migoya, EM, Miller, J, Larson, P, Tanen, M, Hilliard, D, Deacon, C, Gutierrez, M, Stoch, A, Herman, GA, Stein, PP, Holst, JJ, Wagner, JA. Sitagliptin, a selective DPP-4 inhibitor, and metformin have complementary effects to increase active GLP-1 concentrations. Diabetes 56.A74, 2007
195. Holst, JJ, Pedersen, JH, Baldissera, F, Stadil, F. Circulating glucagon after total pancreatectomy in man. Diabetologia 25.396-399, 1983
196. Jackson, RS, Creemers, JW, Farooqi, IS, Raffin-Sanson, ML, Varro, A, Dockray, GJ, Holst, JJ, Brubaker, PL, Corvol, P, Polonsky, KS, Ostrega, D, Becker, KL, Bertagna, X, Hutton, JC, White, A, Dattani, MT, Hussain, K, Middleton, SJ, Nicole, TM, Milla, PJ, Lindley, KJ, O'Rahilly, S. Smallintestinal dysfunction accompanies the complex endocrinopathy of human proprotein convertase 1 deficiency. J Clin Invest 112.1550-1560, 2003
197. Ugleholdt, R, Zhu, X, Deacon, CF, Orskov, C, Steiner, DF, Holst, JJ. Impaired intestinal proglucagon processing in mice lacking prohormone convertase 1. Endocrinology 145.1349-1355, 2004