Absence of glucagon and insulin action reveals a role for the GLP-1 receptor in endogenous glucose production

Diabetes

Volumn 64, Issue 3, 2015, Pages 819-827

  Jun, Lucy S ^a   Millican, Rohn L ^a   Hawkins, Eric D ^a   Konkol, Debra L ^a   Showalter, Aaron D ^a   Christe, Michael E ^a   Michael, M Dodson ^a   Sloop, Kyle W ^a  

^a ELI LILLY AND COMPANY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

GLUCAGON; GLUCAGON LIKE PEPTIDE 1 RECEPTOR; GLUCAGON RECEPTOR; GLUCOSE; INCRETIN; INSULIN; GLUCAGON LIKE PEPTIDE 1; GLUCAGON-LIKE PEPTIDE-1 RECEPTOR; STREPTOZOCIN;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANTIBODY AFFINITY; ARTICLE; CONTROLLED STUDY; GENOTYPE; GLUCAGON RELEASE; GLUCONEOGENESIS; GLUCOSE BLOOD LEVEL; GLUCOSE HOMEOSTASIS; GLUCOSE TOLERANCE; HYPERGLYCEMIA; HYPOINSULINEMIA; INSULIN BLOOD LEVEL; METABOLIC REGULATION; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN BLOOD LEVEL; PROTEIN FUNCTION; REGULATORY MECHANISM; SIGNAL TRANSDUCTION; UPREGULATION; ANIMAL; ANTAGONISTS AND INHIBITORS; DEFICIENCY; GENETICS; IMMUNOHISTOCHEMISTRY; KNOCKOUT MOUSE; METABOLISM;

ANIMALS; GLUCAGON; GLUCAGON-LIKE PEPTIDE 1; GLUCOSE; IMMUNOHISTOCHEMISTRY; INSULIN; MICE; MICE, KNOCKOUT; RECEPTORS, GLUCAGON; STREPTOZOCIN;

EID: 84926432604     PISSN: 00121797     EISSN: 1939327X     Source Type: Journal    
DOI: 10.2337/db14-1052     Document Type: Article

References (48)

1. Ennis ED, Kreisberg RA. Diabetic ketoacidosis and the hyperglycemic hyperosmolar syndrome. In Diabetes Mellitus: a Fundamental and Clinical Text. LeRoith D, Taylor SI, Olefsky JM, Eds. Philadelphia, Lippincott Williams & Wilkins, 2000, p. 336-347
2. Maruyama H, Hisatomi A, Orci L, Grodsky GM, Unger RH. Insulin within islets is a physiologic glucagon release inhibitor. J Clin Invest 1984;74:2296-2299
3. Greenbaum CJ, Havel PJ, Taborsky GJ Jr, Klaff LJ. Intra-islet insulin permits glucose to directly suppress pancreatic A cell function. J Clin Invest 1991;88: 767-773
4. Hope KM, Tran PO, Zhou H, Oseid E, Leroy E, Robertson RP. Regulation of alpha-cell function by the beta-cell in isolated human and rat islets deprived of glucose: the "switch-off" hypothesis. Diabetes 2004;53:1488-1495
5. Banarer S, McGregor VP, Cryer PE. Intraislet hyperinsulinemia prevents the glucagon response to hypoglycemia despite an intact autonomic response. Diabetes 2002;51:958-965
6. Xu E, Kumar M, Zhang Y, et al. Intra-islet insulin suppresses glucagon release via GABA-GABAA receptor system. Cell Metab 2006;3:47-58
7. Meier JJ, Kjems LL, Veldhuis JD, Lefèbvre P, Butler PC. Postprandial suppression of glucagon secretion depends on intact pulsatile insulin secretion: further evidence for the intraislet insulin hypothesis. Diabetes 2006;55:1051-1056
8. Raskin P, Unger RH. Hyperglucagonemia and its suppression - importance in the metabolic control of diabetes. N Engl J Med 1978;299:433-436
9. Dinneen S, Alzaid A, Turk D, Rizza R. Failure of glucagon suppression contributes to postprandial hyperglycaemia in IDDM. Diabetologia 1995;38:337-343
10. Unger RH. The Banting Memorial Lecture 1975. Diabetes and the alpha cell. Diabetes 1976;25:136-151
11. Unger RH, Orci L. The essential role of glucagon in the pathogenesis of diabetes mellitus. Lancet 1975;1:14-16
12. Gelling RW, Du XQ, Dichmann DS, et al. Lower blood glucose, hyperglucagonemia, and pancreatic alpha cell hyperplasia in glucagon receptor knockout mice. Proc Natl Acad Sci U S A 2003;100:1438-1443
13. Parker JC, Andrews KM, Allen MR, Stock JL, McNeish JD. Glycemic control in mice with targeted disruption of the glucagon receptor gene. Biochem Biophys Res Commun 2002;290:839-843
14. Conarello SL, Jiang G, Mu J, et al. Glucagon receptor knockout mice are resistant to diet-induced obesity and streptozotocin-mediated beta cell loss and hyperglycaemia. Diabetologia 2007;50:142-150
15. Eleazu CO, Eleazu KC, Chukwuma S, Essien UN. Review of the mechanism of cell death resulting from streptozotocin challenge in experimental animals, its practical use and potential risk to humans. J Diabetes Metab Disord 2013;12:60
16. Lee Y, Wang MY, Du XQ, Charron MJ, Unger RH. Glucagon receptor knockout prevents insulin-deficient type 1 diabetes in mice. Diabetes 2011;60:391-397
17. 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
18. Gu W, Yan H, Winters KA, et al. Long-term inhibition of the glucagon receptor with a monoclonal antibody in mice causes sustained improvement in glycemic control, with reversible alpha-cell hyperplasia and hyperglucagonemia. J Pharmacol Exp Ther 2009;331:871-881
19. Omar BA, Andersen B, Hald J, Raun K, Nishimura E, Ahrén B. Fibroblast growth factor 21 (FGF21) and glucagon-like peptide 1 contribute to diabetes resistance in glucagon receptor-deficient mice. Diabetes 2014;63:101-110
20. Habegger KM, Stemmer K, Cheng C, et al. Fibroblast growth factor 21 mediates specific glucagon actions. Diabetes 2013;62:1453-1463
21. Arafat AM, Kaczmarek P, Skrzypski M, et al. Glucagon increases circulating fibroblast growth factor 21 independently of endogenous insulin levels: a novel mechanism of glucagon-stimulated lipolysis? Diabetologia 2013;56:588-597
22. Lee Y, Berglund ED, Wang MY, et al. Metabolic manifestations of insulin deficiency do not occur without glucagon action. Proc Natl Acad Sci U S A 2012; 109:14972-14976
23. Campbell JE, Drucker DJ. Pharmacology, physiology, and mechanisms of incretin hormone action. Cell Metab 2013;17:819-837
24. Jun LS, Showalter AD, Ali N, et al. A novel humanized GLP-1 receptor model enables both affinity purification and Cre-LoxP deletion of the receptor. PLoS ONE 2014;9:e93746
25. Korytko AI, Millican RL. Glucagon receptor antagonists. U.S. patent US7968686 B2. Eli Lilly and Company, 28 June 2011
26. Perfetti R, Hui H. The role of GLP-1 in the life and death of pancreatic beta cells. Horm Metab Res 2004;36:804-810
27. Doyle ME, Egan JM. Mechanisms of action of glucagon-like peptide 1 in the pancreas. Pharmacol Ther 2007;113:546-593
28. 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 2003; 278:471-478
29. Rondas D, Bugliani M, D'Hertog W, et al. Glucagon-like peptide-1 protects human islets against cytokine-mediated b-cell dysfunction and death: a proteomic study of the pathways involved. J Proteome Res 2013;12:4193-4206
30. Pederson RA, Satkunarajah M, McIntosh CH, et al. Enhanced glucosedependent insulinotropic polypeptide secretion and insulinotropic action in glucagon-like peptide 1 receptor-/-mice. Diabetes 1998;47:1046-1052
31. Richards P, Parker HE, Adriaenssens AE, et al. Identification and characterization of GLP-1 receptor-expressing cells using a new transgenic mouse model. Diabetes 2014;63:1224-1233
32. Ayala JE, Bracy DP, James FD, Julien BM, Wasserman DH, Drucker DJ. The glucagon-like peptide-1 receptor regulates endogenous glucose production and muscle glucose uptake independent of its incretin action. Endocrinology 2009; 150:1155-1164
33. D'Alessio D, Vahl T, Prigeon R. Effects of glucagon-like peptide 1 on the hepatic glucose metabolism. Horm Metab Res 2004;36:837-841
34. Dardevet D, Moore MC, DiCostanzo CA, et al. Insulin secretion-independent effects of GLP-1 on canine liver glucose metabolism do not involve portal vein GLP-1 receptors. Am J Physiol Gastrointest Liver Physiol 2005;289:G806-G814
35. Dhanesha N, Joharapurkar A, Shah G, et al. Exendin-4 reduces glycemia by increasing liver glucokinase activity: an insulin independent effect. Pharmacol Rep 2012;64:140-149
36. Gerich JE, Lorenzi M, Bier DM, et al. Prevention of human diabetic ketoacidosis by somatostatin. Evidence for an essential role of glucagon. N Engl J Med 1975;292:985-989
37. Cherrington AD, Lacy WW, Chiasson JL. Effect of glucagon on glucose production during insulin deficiency in the dog. J Clin Invest 1978;62:664-677
38. Unger RH, Cherrington AD. Glucagonocentric restructuring of diabetes: a pathophysiologic and therapeutic makeover. J Clin Invest 2012;122:4-12
39. Longuet C, Robledo AM, Dean ED, et al. Liver-specific disruption of the murine glucagon receptor produces a-cell hyperplasia: evidence for a circulating a-cell growth factor. Diabetes 2013;62:1196-1205
40. Wilson-Pérez HE, Chambers AP, Ryan KK, et al. Vertical sleeve gastrectomy is effective in two genetic mouse models of glucagon-like Peptide 1 receptor deficiency. Diabetes 2013;62:2380-2385
41. Hansotia T, Baggio LL, Delmeire D, et al. Double incretin receptor knockout (DIRKO) mice reveal an essential role for the enteroinsular axis in transducing the glucoregulatory actions of DPP-IV inhibitors. Diabetes 2004;53: 1326-1335
42. Prigeon RL, Quddusi S, Paty B, D'Alessio DA. Suppression of glucose production by GLP-1 independent of islet hormones: a novel extrapancreatic effect. Am J Physiol Endocrinol Metab 2003;285:E701-E707
43. Burmeister MA, Ferre T, Ayala JE, King EM, Holt RM, Ayala JE. Acute activation of central GLP-1 receptors enhances hepatic insulin action and insulin secretion in high-fat-fed, insulin resistant mice. Am J Physiol Endocrinol Metab 2012;302:E334-E343
44. Kielgast U, Krarup T, Holst JJ, Madsbad S. Four weeks of treatment with liraglutide reduces insulin dose without loss of glycemic control in type 1 diabetic patients with and without residual beta-cell function. Diabetes Care 2011;34: 1463-1468
45. Varanasi A, Bellini N, Rawal D, et al. Liraglutide as additional treatment for type 1 diabetes. Eur J Endocrinol 2011;165:77-84
46. Ghazi T, Rink L, Sherr JL, Herold KC. Acute metabolic effects of exenatide in patients with type 1 diabetes with and without residual insulin to oral and intravenous glucose challenges. Diabetes Care 2014;37:210-216
47. Engel SS, Xu L, Andryuk PJ, et al. Efficacy and tolerability of MK-0893, a glucagon receptor antagonist (GRA), in patients with type 2 diabetes (T2DM) [abstract 0309-OR]. Presented at the 71st Scientific Sessions of the American Diabetes Association, 24-28 June 2011, San Diego, CA
48. Kazda C, Headlee S, Ding Y, et al. The glucagon receptor antagonist LY2409021 significantly lowers HbA1c and is well tolerated in patients with T2DM - a 24-week phase 2 study [abstract 112-OR/0112]. Presented at the 73rd Scientific Sessions of the American Diabetes Association, 21-25 June 2013, Chicago, IL