Dogfish glucagon analogues counter hyperglycaemia and enhance both insulin secretion and action in diet-induced obese diabetic mice

Diabetes, Obesity and Metabolism

Volumn 18, Issue 10, 2016, Pages 1013-1024

  O'Harte, F P M ^a   Ng, M T ^a   Lynch, A M ^a   Conlon, J M ^a   Flatt, P R ^a  

^a UNIVERSITY OF ULSTER   (United Kingdom)

Author keywords

chronic study; co agonist; diabetic mice; dogfish glucagon; glucagon like peptide 1; peptide analogues; therapy

Indexed keywords

AMYLASE; CHOLESTEROL; DOGFISH GLUCAGON; DOGFISH GLUCAGON EXENDIN 4 (31-39); DOGFISH GLUCAGON LYSINE 30 GAMMA GLUTAMYL PAL; EXENDIN 4; GLUCAGON; GLUCAGON DERIVATIVE; GLUCOSE; HIGH DENSITY LIPOPROTEIN CHOLESTEROL; INSULIN; LOW DENSITY LIPOPROTEIN CHOLESTEROL; TRIACYLGLYCEROL; UNCLASSIFIED DRUG; GLUCOSE BLOOD LEVEL;

AMINO ACID SEQUENCE; AMYLASE BLOOD LEVEL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTIDIABETIC ACTIVITY; AREA UNDER THE CURVE; ARTICLE; CHOLESTEROL BLOOD LEVEL; CHRONIC DRUG ADMINISTRATION; CONTROLLED STUDY; DIET INDUCED OBESITY; ENERGY EXPENDITURE; EXPERIMENTAL DIABETES MELLITUS; FOOD INTAKE; GLUCOSE BLOOD LEVEL; GLUCOSE TOLERANCE TEST; GLYCEMIC CONTROL; HYPERGLYCEMIA; IN VIVO STUDY; INSULIN BLOOD LEVEL; INSULIN LIKE ACTIVITY; INSULIN RELEASE; INSULIN RESISTANCE; INSULIN SENSITIVITY; LIPID DIET; LIPID METABOLISM; LUNG GAS EXCHANGE; MALE; MOLECULAR WEIGHT; MOUSE; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; OXYGEN CONSUMPTION; PANCREAS ISLET BETA CELL; RECEPTOR DOWN REGULATION; TRIACYLGLYCEROL BLOOD LEVEL; TUCK ORDINARY MOUSE; WEIGHT CHANGE; ANALOGS AND DERIVATIVES; ANIMAL; COMPLICATION; DOGFISH; DRUG EFFECTS; METABOLISM; MOUSE MUTANT; OBESITY; PATHOLOGY; PHYSIOLOGY; SECRETION (PROCESS);

ANIMALS; BLOOD GLUCOSE; DIABETES MELLITUS, EXPERIMENTAL; DIET, HIGH-FAT; DOGFISH; GLUCAGON; GLUCOSE TOLERANCE TEST; HYPERGLYCEMIA; INSULIN; INSULIN RESISTANCE; INSULIN-SECRETING CELLS; MALE; MICE; MICE, OBESE; OBESITY;

EID: 84981484204     PISSN: 14628902     EISSN: 14631326     Source Type: Journal    
DOI: 10.1111/dom.12713     Document Type: Article

References (54)

1. Davidson JA, Holland WL, Roth MG, et al. Glucagon therapeutics, dawn of a new era for diabetes care. Diabetes Metab Res Rev. 2016, DOI: 10.1002/dmrr.2773. Review [Epub ahead of print].
2. Unger RH, Cherrington AD. Glucagonocentric restructuring of diabetes: a pathophysiologic and therapeutic makeover. J Clin Invest. 2012;122:4–12.
3. Farhy LS, McCall AL. Optimizing reduction in basal hyperglucagonaemia to repair defective glucagon counterregulation in insulin deficiency. Diabetes Obes Metab. 2011;13:133–143.
4. Campbell JE, Drucker DJ. Islet α cells and glucagon-critical regulators of energy homeostasis. Nat Rev Endocrinol. 2015;11:329–338.
5. Gelling RW, Du XQ, Dichmann DS, et al. Lower blood glucose, hyperglucagonemia, and pancreatic α cell hyperplasia in glucagon receptor knockout mice. Proc Natl Acad Sci U S A. 2003;100:1438–1443.
6. Sadry SA, Drucker DJ. Emerging combinatorial hormone therapies for the treatment of obesity and T2DM. Nat Rev Endocrinol. 2013;9:425–433.
7. Charron MJ, Vuguin PM. Lack of glucagon receptor signaling and its implications beyond glucose homeostasis. J Endocrinol. 2015;224:R123–R130.
8. Ye L, Robertson MA, Hesselson D, Stainier DY, Anderson RM. Glucagon is essential for alpha cell transdifferentiation and beta cell neogenesis. Development. 2015;142:1407–1417.
9. Holst JJ. Treatment of type 2 diabetes mellitus with agonists of the GLP-1 receptor or DPP-IV inhibitors. Expert Opin Emerg Drugs. 2004;9:155–166.
10. Campbell JE, Drucker DJ. Pharmacology, physiology, and mechanisms of incretin hormone action. Cell Metab. 2013;17:819–837.
11. Nauck M. Incretin therapies: highlighting common features and differences in the modes of action of glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors. Diabetes Obes Metab. 2016;18:203–216.
12. 8-substituted GLP-1 analogues. Biol Chem. 2004;385:169–177.
13. Drucker DJ. Incretin action in the pancreas: potential promise, possible perils, and pathological pitfalls. Diabetes. 2013;62:3316–3323.
14. Irwin N, Flatt PR. New perspectives on exploitation of incretin peptides for the treatment of diabetes and related disorders. World J Diabetes. 2015;6:1285–1295.
15. Madsbad S. Exenatide and liraglutide: different approaches to develop GLP-1 receptor agonists (incretin mimetics)–preclinical and clinical results. Best Pract Res Clin Endocrinol Metab. 2009;23:463–477.
16. Nikfar S, Abdollahi M, Salari P. The efficacy and tolerability of exenatide in comparison to placebo; a systematic review and meta-analysis of randomized clinical trials. J Pharm Pharm Sci. 2012;15:1–30.
17. Kela R, Davies MJ. Treatment evaluation of liraglutide in type 2 diabetes. Expert Opin Biol Ther. 2012;12:1551–1556.
18. Wysham C, Grimm M, Chen S. Once weekly exenatide: efficacy, tolerability and place in therapy. Diabetes Obes Metab. 2013;15:871–881.
19. McCormack PL. Exenatide twice daily: a review of its use in the management of patients with type 2 diabetes mellitus. Drugs. 2014;74:325–351.
20. Scott LJ. Liraglutide: a review of its use in adult patients with type 2 diabetes mellitus. Drugs. 2014;74:2161–2174.
21. Irwin N, Pathak V, Flatt PR. A novel CCK-8/GLP-1 hybrid peptide exhibiting prominent insulinotropic, glucose-lowering, and satiety actions with significant therapeutic potential in high-fat-fed mice. Diabetes. 2015;64:2996–3009.
22. Bhat VK, Kerr BD, Flatt PR, Gault VA. A novel GIP-oxyntomodulin hybrid peptide acting through GIP, glucagon and GLP-1 receptors exhibits weight reducing and anti-diabetic properties. Biochem Pharmacol. 2013a;85:1655–1662.
23. Bhat VK, Kerr BD, Vasu S, Flatt PR, Gault VA. A DPP-IV-resistant triple-acting agonist of GIP, GLP-1 and glucagon receptors with potent glucose-lowering and insulinotropic actions in high-fat-fed mice. Diabetologia. 2103b;56:1417–1424.
24. Tom I, Lee V, Dumas M, et al. Reproducible production of a PEGylated dual-acting peptide for diabetes. AAPS J. 2007;9:E227–E234.
25. Franklin ZJ, McDonnell B, Montgomery IA, Flatt PR, Irwin N. Dual modulation of GIP and glucagon action by the low molecular weight compound 4-hydroxybenzoic acid 2-bromobenzylidene hydrazide. Diabetes Obes Metab. 2011;13:742–749.
26. Fosgerau K, Jessen L, Lind Tolborg J, et al. The novel GLP-1-gastrin dual agonist, ZP3022, increases β-cell mass and prevents diabetes in db/db mice. Diabetes Obes Metab. 2013;15:62–71.
27. Trevaskis JL, Mack CM, Sun C, et al. Improved glucose control and reduced body weight in rodents with dual mechanism of action peptide hybrids. PLoS One. 2013;8:e78154.
28. Finan B, Ma T, Ottaway N, et al. Unimolecular dual incretins maximize metabolic benefits in rodents, monkeys, and humans. Sci Transl Med. 2013;5:209ra151.
29. Skarbaliene J, Secher T, Jelsing J, et al. The anti-diabetic effects of GLP-1-gastrin dual agonist ZP3022 in ZDF rats. Peptides. 2015;69:47–55.
30. Kerr BD, Flatt PR, Gault VA. (D-Ser2)Oxm[mPEG-PAL]: a novel chemically modified analogue of oxyntomodulin with antihyperglycaemic, insulinotropic and anorexigenic actions. Biochem Pharmacol. 2010;80:1727–1735.
31. Patel V, Joharapurkar A, Dhanesha N, et al. Co-agonist of glucagon and GLP-1 reduces cholesterol and improves insulin sensitivity independent of its effect on appetite and body weight in diet-induced obese C57 mice. Can J Physiol Pharmacol. 2013;91:1009–1015.
32. Tan TM, Field BC, McCullough KA, et al. Coadministration of glucagon-like peptide-1 during glucagon infusion in humans results in increased energy expenditure and amelioration of hyperglycemia. Diabetes. 2013;62:1131–1138.
33. Pocai A, Carrington PE, Adams JR, et al. Glucagon-like peptide 1/glucagon receptor dual agonism reverses obesity in mice. Diabetes. 2009;58:2258–2266.
34. Irwin N, Green BD, Mooney MH, et al. A novel, long-acting agonist of glucose-dependent insulinotropic polypeptide suitable for once-daily administration in type 2 diabetes. J Pharmacol Exp Ther. 2005;314:1187–1194.
35. Gault VA, Kerr BD, Harriott P, Flatt PR. Administration of an acylated GLP-1 and GIP preparation provides added beneficial glucose-lowering and insulinotropic actions over single incretins in mice with Type 2 diabetes and obesity. Clin Sci (London). 2011b;121:107–117.
36. Gault VA, Bhat VK, Irwin N, Flatt PR. A novel glucagon-like peptide-1 (GLP-1)/glucagon hybrid peptide with triple-acting agonist activity at glucose-dependent insulinotropic polypeptide, GLP-1, and glucagon receptors and therapeutic potential in high fat-fed mice. J Biol Chem. 2013;288:35581–25591.
37. Conlon JM, O'Toole L, Thim L. Primary structure of glucagon from the gut of the common dogfish, Scyliorhinus canicula. FEBS Lett. 1987;214:50–56.
38. O'Harte FPM, Ng MT, Lynch AM, Conlon JM, Flatt PR. Novel dual agonist peptide analogues derived from dogfish glucagon show promising in vitro insulin releasing actions and antihyperglycaemic activity in mice. Mol Cell Endocrinol. 2016;431:133–144.
39. Gault VA, Porter DW, Irwin N, Flatt PR. Comparison of sub-chronic metabolic effects of stable forms of naturally occurring GIP(1-30) and GIP(1-42) in high-fat fed mice. J Endocrinol. 2011;208:265–271.
40. Holz GG, Chepurny OG. Glucagon-like peptide-1 synthetic analogs: new therapeutic agents for use in the treatment of diabetes mellitus. Curr Med Chem. 2003;10:2471–2483.
41. Knudsen LB. Glucagon-like peptide-1: the basis of a new class of treatment for type 2 diabetes. J Med Chem. 2004;47:4128–4134.
42. Flatt PR, Bailey CJ. Development of glucose intolerance and impaired plasma insulin response to glucose in obese hyperglycaemic (ob/ob) mice. Horm Metab Res. 1981;13:556–560.
43. Lynch AM, Pathak N, Flatt YE, et al. Comparison of stability, cellular, glucose-lowering and appetite supressing effects of oxyntomodulin analogues modified at the N-terminus. Eur J Pharmacol. 2014;743:69–78.
44. Vasu S, Moffett RC, Thorens B, Flatt PR. Role of endogenous GLP-1 and GIP in beta cell compensatory responses to insulin resistance and cellular stress. PLoS One. 2014;9:e101005.
45. Moffett RC, Irwin N, Francis JM, Flatt PR. Alterations of glucose-dependent insulinotropic polypeptide and expression of genes involved in mammary gland and adipose tissue lipid metabolism during pregnancy and lactation. PLoS One. 2013;8:e78560.
46. Day JW, Ottaway N, Patterson JT, et al. A new glucagon and GLP-1 co-agonist eliminates obesity in rodents. Nat Chem Biol. 2009;5:749–757.
47. Buettner R, Schölmerich J, Bollheimer LC. High-fat diets: modeling the metabolic disorders of human obesity in rodents. Obesity (Silver Spring). 2007;15:798–808.
48. Irwin N, McClean PL, Cassidy RS, et al. Comparison of the anti-diabetic effects of GIP- and GLP-1-receptor activation in obese diabetic (ob/ob) mice: studies with DPP IV resistant N-AcGIP and exendin(1-39)amide. Diabetes Metab Res Rev. 2007;23:572–579.
49. Irwin N, Hunter K, Frizzell N, Flatt PR. Antidiabetic effects of sub-chronic activation of the GIP receptor alone and in combination with background exendin-4 therapy in high fat fed mice. Regul Pept. 2009;153:70–76.
50. Gier B, Matveyenko AV, Kirakossian D, Dawson D, Dry SM, Butler PC. Chronic GLP-1 receptor activation by exendin-4 induces expansion of pancreatic duct glands in rats and accelerates formation of dysplastic lesions and chronic pancreatitis in the Kras(G12D) mouse model. Diabetes. 2012;61:1250–1262.
51. Rouse R, Xu L, Stewart S, Zhang J. High fat diet and GLP-1 drugs induce pancreatic injury in mice. Toxicol Appl Pharmacol. 2014;276:104–114.
52. Moffett RC, Vasu S, Flatt PR. Functional GIP receptors play a major role in islet compensatory response to high fat feeding in mice. Biochim Biophys Acta. 1850;2015:1206–1214.
53. Lee J, Lee C, Kim I, et al. Preparation and evaluation of palmitic acid-conjugated exendin-4 with delayed absorption and prolonged circulation for longer hypoglycemia. Int J Pharm. 2012;424:50–57.
54. Habegger KM, Heppner KM, Geary N, Bartness TJ, DiMarchi R, Tschöp MH. The metabolic actions of glucagon revisited. Nat Rev Endocrinol. 2010;6:689–697.