Regulation of glucagon secretion by incretins

Diabetes, Obesity and Metabolism

Volumn 13, Issue SUPPL. 1, 2011, Pages 89-94

  Holst, J ^a,b,c   Christensen, M ^a,b,c   Lund, A ^a,b,c   De Heer, J ^a,c   Svendsen, B ^a,c   Kielgast, U ^a,c   Knop, F K ^b,c  

^a UNIVERSITY OF COPENHAGEN   (Denmark)

^b GENTOFTE UNIVERSITY HOSPITAL   (Denmark)

^c UNIVERSITY OF COPENHAGEN   (Denmark)

Author keywords

Glucagon assay; Glucagon like peptide (GLP 1); Glucose dependent insulinotropic polypeptide (GIP); Proglucagon processing

Indexed keywords

DIPEPTIDYL PEPTIDASE IV INHIBITOR; EXENDIN 4; GASTRIC INHIBITORY POLYPEPTIDE; GASTROINTESTINAL HORMONE; GLUCAGON; GLUCAGON LIKE PEPTIDE 1; GLUCAGON LIKE PEPTIDE 1 RECEPTOR; GLUCAGON LIKE PEPTIDE 2; GLUCOSE; INCRETIN; INSULIN;

DIET RESTRICTION; GLUCAGON RELEASE; GLUCONEOGENESIS; GLUCOSE METABOLISM; HORMONE INHIBITION; HORMONE RELEASE; HUMAN; HYPERGLUCAGONEMIA; HYPERGLYCEMIA; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; PANCREAS ISLET ALPHA CELL; PARACRINE SIGNALING; POSTPRANDIAL STATE; REVIEW; SOMATOSTATIN CELL;

EID: 79961191559     PISSN: 14628902     EISSN: 14631326     Source Type: Journal    
DOI: 10.1111/j.1463-1326.2011.01452.x     Document Type: Review

References (53)

1. Toft-Nielsen MB, Damholt MB, Madsbad S et al. Determinants of the impaired secretion of glucagon-like peptide-1 in type 2 diabetic patients. J Clin Endocrinol Metab 2001; 86: 3717-3723.
2. 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 1987; 36: 274-283.
3. 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 2000; 85: 4053-4059.
4. Holst JJ, Vilsboll T, Deacon CF. The incretin system and its role in type 2 diabetes mellitus. Mol Cell Endocrinol 2009; 297: 127-136.
5. Jaspan JB, Polonsky KS, Rojdmark S, Ishida T, Field JB, Rubenstein AH. Hepatic extraction of plasma immunoreactive glucagon components. Predilection for 3500-dalton glucagon metabolism by the liver. Diabetes 1981; 30: 767-772.
6. Holst JJ. Degradation of glucagons. In: Henriksen JH, ed. Degradation of Bioactive Substances: Physiology and Pathophysiology. CRC Press, Inc., Boca Raton, FL, 1991; 167-180.
7. Deacon CF, Kelstrup M, Trebbien R, Klarskov L, Olesen M, Holst JJ. Differential regional metabolism of glucagon in anesthetized pigs. Am J Physiol Endocrinol Metab 2003; 285: E552-560.
8. 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. Diabetes Metab 1980; 6: 117-127.
9. Holst JJ, Bersani M, Johnsen AH, Kofod H, Hartmann B, Orskov C. Proglucagon processing in porcine and human pancreas. J Biol Chem 1994; 269: 18827-18833.
10. Baldissera FG, Holst JJ. Glicentin 1-61 probably represents a major fraction of glucagon-related peptides in plasma of anaesthetized uraemic pigs. Diabetologia 1986; 29: 462-467.
11. Holst JJ. Glucagon and glucagon-like peptides 1 and 2. Results Probl Cell Differ 2010; 50: 121-135.
12. Holst JJ. Molecular heterogeneity of glucagon in normal subjects and in patients with glucagon-producing tumours. Diabetologia 1983; 24: 359-365.
13. Holst JJ, Pedersen JH, Baldissera F, Stadil F. Circulating glucagon after total pancreatectomy in man. Diabetologia 1983; 25: 396-399.
14. Lefebvre PJ, Luyckx AS. Neurotransmitters and glucagon release from the isolated, perfused canine stomach. Diabetes 1980; 29: 697-701.
15. Holst JJ, Aggestrup S, Loud FB, Olesen M. Content and gel filtration profiles of glucagon-like and somatostatin-like immunoreactivity in human fundic mucosa. J Clin Endocrinol Metab 1983; 56: 729-732.
16. 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 2002; 45: 1111-1119.
17. Knop FK, Vilsboll T, Hojberg PV et al. Reduced incretin effect in type 2 diabetes: cause or consequence of the diabetic state? Diabetes 2007; 56: 1951-1959.
18. 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 2007; 50: 797-805.
19. Knop FK, Vilsboll T, Larsen S, Madsbad S, Holst JJ, Krarup T. Glucagon suppression during OGTT worsens while suppression during IVGTT sustains alongside development of glucose intolerance in patients with chronic pancreatitis. Regul Pept 2010; 164: 144-150.
20. Hansen KB, Vilsboll T, Bagger JI, Holst JJ, Knop FK. Increased postprandial GIP and glucagon responses, but unaltered GLP-1 response after intervention with steroid hormone, relative physical inactivity, and high-calorie diet in healthy subjects. J Clin Endocrinol Metab 2011; 96: 447-453.
21. Hare KJ, Vilsboll T, Holst JJ, Knop FK. Inappropriate glucagon response after oral compared with isoglycemic intravenous glucose administration in patients with type 1 diabetes. Am J Physiol Endocrinol Metab 2010; 298: E832-837.
22. Bagger JI, Knop FK, Lund A, Vestergaard H, Holst JJ, Vilsboll T. Impaired regulation of the incretin effect in patients with type 2 diabetes. J Clin Endocrinol Metab 2011; 96: 737-745.
23. Knop FK, Bagger JI, Lund A, Vestergaard H, Holst JJ, Vilsboll T. Glucagon responses to increasing oral loads of glucose and corresponding isoglycemic intravenous glucose infusions in patients with type 2 diabetes and healthy subjects. Diabetes 2009; 58(S1): A368.
24. Hare KJ, Knop FK, Asmar M et al. Preserved inhibitory potency of GLP-1 on glucagon secretion in type 2 diabetes mellitus. J Clin Endocrinol Metab 2009; 94: 4679-4687.
25. 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 2003; 27: 450-456.
26. Meier JJ, Nauck MA, Pott A et al. Glucagon-like peptide 2 stimulates glucagon secretion, enhances lipid absorption, and inhibits gastric acid secretion in humans. Gastroenterology 2006; 130: 44-54.
27. Meier JJ, Gallwitz B, Siepmann N et al. Gastric inhibitory polypeptide (GIP) dose-dependently stimulates glucagon secretion in healthy human subjects at euglycaemia. Diabetologia 2003; 46: 798-801.
28. Lund A, Vilsboll T, Bagger JI, Holst JJ, Knop FK. The separate and combined impact of the intestinal hormones, GIP, GLP-1 and GLP-2, on glucagon secretion in type 2 diabetes. Am J Physiol Endocrinol Metab 2011; 300: E1038-1046.
29. Heller RS, Kieffer TJ, Habener JF. Insulinotropic glucagon-like peptide I receptor expression in glucagon-producing alpha-cells of the rat endocrine pancreas. Diabetes 1997; 46: 785-791.
30. Moens K, Heimberg H, Flamez D et al. Expression and functional activity of glucagon, glucagon-like peptide I, and glucose-dependent insulinotropic peptide receptors in rat pancreatic islet cells. Diabetes 1996; 45: 257-261.
31. 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 2008; 56: 841-851.
32. De Marinis YZ, Salehi A, Ward CE et al. GLP-1 inhibits and adrenaline stimulates glucagon release by differential modulation of N- and L-type Ca2+ channel-dependent exocytosis. Cell Metab 2010; 11: 543-553.
33. 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 1997; 46: 792-800.
34. 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 1988; 123: 2009-2013.
35. Kreymann B, Williams G, Ghatei MA, Bloom SR. Glucagon-like peptide-1 7-36: a physiological incretin in man. Lancet 1987; 2: 1300-1304.
36. 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 2003; 114: 115-121.
37. Hvidberg A, Nielsen MT, Hilsted J, Orskov C, Holst JJ. Effect of glucagon-like peptide-1 (proglucagon 78-107 amide) on hepatic glucose production in healthy man. Metabolism 1994; 43: 104-108.
38. Edwards CM, Todd JF, Mahmoudi M et al. Glucagon-like peptide 1 has a physiological role in the control of postprandial glucose in humans: studies with the antagonist exendin 9-39. Diabetes 1999; 48: 86-93.
39. Kielgast U, Holst JJ, Madsbad S. Antidiabetic actions of endogenous and exogenous glp-1 in type 1 diabetic patients with and without residual β-cell function. Diabetes 2011; 60: 1599-1607.
40. Toft-Nielsen M, Madsbad S, Holst JJ. The effect of glucagon-like peptide I (GLP-I) on glucose elimination in healthy subjects depends on the pancreatic glucoregulatory hormones. Diabetes 1996; 45: 552-556.
41. 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 1996; 19: 580-586.
42. Kielgast U, Asmar M, Madsbad S, Holst JJ. Effect of glucagon-like peptide-1 on alpha- and beta-cell function in C-peptide-negative type 1 diabetic patients. J Clin Endocrinol Metab 2010; 95: 2492-2496.
43. Samols E, Bonner-Weir S, Weir GC. Intra-islet insulin-glucagon-somatostatin relationships. Clin Endocrinol Metab 1986; 15: 33-58.
44. Bosco D, Armanet M, Morel P et al. Unique arrangement of alpha- and beta-cells in human islets of Langerhans. Diabetes 2010; 59: 1202-1210.
45. Gelling RW, Vuguin PM, Du XQ et al. Pancreatic beta-cell overexpression of the glucagon receptor gene results in enhanced beta-cell function and mass. Am J Physiol Endocrinol Metab 2009; 297: E695-707.
46. Sloop KW, Cao JX, Siesky AM et al. Hepatic and glucagon-like peptide-1-mediated reversal of diabetes by glucagon receptor antisense oligonucleotide inhibitors. J Clin Invest 2004; 113: 1571-1581.
47. Holst JJ, Deacon CF. Glucagon-like peptide-1 mediates the therapeutic actions of DPP-IV inhibitors. Diabetologia 2005; 48: 612-615.
48. Balkan B, Li X. Portal GLP-1 administration in rats augments the insulin response to glucose via neuronal mechanisms. Am J Physiol Regul Integr Comp Physiol 2000; 279: R1449-1454.
49. Holst JJ, Schwartz TW, Knuhtsen S, Jensen SL, Nielsen OV. Autonomic nervous control of the endocrine secretion from the isolated, perfused pig pancreas. J Auton Nerv Syst 1986; 17: 71-84.
50. Wettergren A, Wojdemann M, Holst JJ. Glucagon-like peptide-1 inhibits gastropancreatic function by inhibiting central parasympathetic outflow. Am J Physiol 1998; 275: G984-992.
51. de Heer J, Rasmussen C, Coy DH, Holst JJ. Glucagon-like peptide-1, but not glucose-dependent insulinotropic peptide, inhibits glucagon secretion via somatostatin (receptor subtype 2) in the perfused rat pancreas. Diabetologia 2008; 51: 2263-2270.
52. Hansen M, Knop FK, Hare KJ, Holst JJ. Inhibition of glucagon secretion by GLP-1 agonists and DPP4 inhibitors. Médecine des Maladies Métaboliques. In press.
53. Hare KJ, Vilsboll T, Asmar M, Deacon CF, Knop FK, Holst JJ. The glucagonostatic and insulinotropic effects of glucagon-like peptide 1 contribute equally to its glucose-lowering action. Diabetes 2010; 59: 1765-1770.