The glucagon receptor is involved in mediating the body weight-lowering effects of oxyntomodulin

Obesity

Volumn 20, Issue 8, 2012, Pages 1566-1571

  Kosinski, Jennifer R ^a   Hubert, James ^a   Carrington, Paul E ^a   Chicchi, Gary G ^a   Mu , James ^a   Miller, Corey ^a   Cao, Jin ^a   Bianchi , Elisabetta ^b,c   Pessi, Antonello ^b,d   Sinharoy, Ranabir ^a   Marsh, Donald J ^a   Pocai, Alessandro ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

^b IRBM   (Italy)

^c IRBM Science Park   (Italy)

^d PeptiPharma   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

GLUCAGON LIKE PEPTIDE 1 RECEPTOR; GLUCAGON LIKE PEPTIDE 1 RECEPTOR AGONIST; GLUCAGON RECEPTOR; OXYNTOMODULIN;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTIDIABETIC ACTIVITY; ANTIOBESITY ACTIVITY; ARTICLE; CONTROLLED STUDY; DIETARY INTAKE; DRUG ACTIVITY; DRUG EFFICACY; DRUG MECHANISM; ENZYME ACTIVATION; ENZYME INHIBITION; FEMALE; GLYCOGENOLYSIS; IN VITRO STUDY; MALE; NONHUMAN; OBESITY; RAT; TREATMENT RESPONSE; WEIGHT REDUCTION;

ANIMALS; ANTI-OBESITY AGENTS; ENERGY INTAKE; GLUCAGON; GLYCOGENOLYSIS; HUMANS; HYPOGLYCEMIC AGENTS; HYPOLIPIDEMIC AGENTS; LIVER; MALE; MICE; MICE, INBRED C57BL; MICE, KNOCKOUT; MICE, OBESE; OBESITY; OXYNTOMODULIN; RECEPTORS, GLUCAGON; WEIGHT LOSS;

MUS; RODENTIA;

EID: 84864351901     PISSN: 19307381     EISSN: 1930739X     Source Type: Journal    
DOI: 10.1038/oby.2012.67     Document Type: Article

References (31)

1. Wynne K, Park AJ, Small CJ et al. Subcutaneous oxyntomodulin reduces body weight in overweight and obese subjects: a double-blind, randomized, controlled trial. Diabetes 2005;54:2390-2395.
2. Dakin CL, Gunn I, Small CJ et al. Oxyntomodulin inhibits food intake in the rat. Endocrinology 2001;142:4244-4250.
3. Baggio LL, Huang Q, Brown TJ, Drucker DJ. Oxyntomodulin and glucagonlike peptide-1 differentially regulate murine food intake and energy expenditure. Gastroenterology 2004;127:546-558.
4. Wynne K, Park AJ, Small CJ et al. Oxyntomodulin increases energy expenditure in addition to decreasing energy intake in overweight and obese humans: a randomised controlled trial. Int J Obes (Lond) 2006;30: 1729-1736.
5. Baldissera FG, Holst JJ, Knuhtsen S, Hilsted L, Nielsen OV. Oxyntomodulin (glicentin-(33-69)): pharmacokinetics, binding to liver cell membranes, effects on isolated perfused pig pancreas, and secretion from isolated perfused lower small intestine of pigs. Regul Pept 1988;21:151-166.
6. 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.
7. Gros L, Thorens B, Bataille D, Kervran A. Glucagon-like peptide-1-(7-36) amide, oxyntomodulin, and glucagon interact with a common receptor in a somatostatin-secreting cell line. Endocrinology 1993;133:631-638.
8. Sowden GL, Drucker DJ, Weinshenker D, Swoap SJ. Oxyntomodulin increases intrinsic heart rate in mice independent of the glucagonlike peptide-1 receptor. Am J Physiol Regul Integr Comp Physiol 2007;292:R962-R970.
9. Wynne K, Field BC, Bloom SR. The mechanism of action for oxyntomodulin in the regulation of obesity. Curr Opin Investig Drugs 2010;11:1151-1157.
10. Maida A, Lovshin JA, Baggio LL, Drucker DJ. The glucagon-like peptide-1 receptor agonist oxyntomodulin enhances beta-cell function but does not inhibit gastric emptying in mice. Endocrinology 2008;149:5670-5678.
11. Habegger KM, Heppner KM, Geary N et al. The metabolic actions of glucagon revisited. Nat Rev Endocrinol 2010;6:689-697.
12. Salter JM. Metabolic effects of glucagon in the Wistar rat. Am J Clin Nutri 1960;8:535-539.
13. Salter JM, Ezrin C, Laidlaw JC, Gornall AG. Metabolic effects of glucagon in human subjects. Metab Clin Exp 1960;9:753-768.
14. Langhans W, Zeiger U, Scharrer E, Geary N. Stimulation of feeding in rats by intraperitoneal injection of antibodies to glucagon. Science 1982;218: 894-896.
15. PENICK SB, HINKLE LE Jr. Depression of food intake induced in healthy subjects by glucagon. N Engl J Med 1961;264:893-897.
16. Schulman JL, Carleton JL, Whitney G, Whitehorn JC. Effect of glucagon on food intake and body weight in man. J Appl Physiol 1957;11:419-421.
17. Orskov C, Wettergren A, Holst JJ. Biological effects and metabolic rates of glucagonlike peptide-1 7-36 amide and glucagonlike peptide-1 7-37 in healthy subjects are indistinguishable. Diabetes 1993;42:658-661.
18. Kervran A, Blache P, Bataille D. Distribution of oxyntomodulin and glucagon in the gastrointestinal tract and the plasma of the rat. Endocrinology 1987;121:704-713.
19. Dallas-Yang Q, Shen X, Strowski M et al. Hepatic glucagon receptor binding and glucose-lowering in vivo by peptidyl and non-peptidyl glucagon receptor antagonists. Eur J Pharmacol 2004;501:225-234.
20. Scrocchi LA, Brown TJ, MaClusky N et al. Glucose intolerance but normal satiety in mice with a null mutation in the glucagon-like peptide 1 receptor gene. Nat Med 1996;2:1254-1258.
21. Mu J, Jiang G, Brady E et al. Preclinical efficacy and mechanism of action of a potent small molecule glucagon receptor antagonist. Diabetes 2010;59:A1533.
22. Turton MD, O'Shea D, Gunn I et al. A role for glucagon-like peptide-1 in the central regulation of feeding. Nature 1996;379:69-72.
23. 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 2002;22:10470-10476.
24. Meier JJ, Gallwitz B, Schmidt WE, Nauck MA. Glucagon-like peptide 1 as a regulator of food intake and body weight: therapeutic perspectives. Eur J Pharmacol 2002;440:269-279.
25. Dakin CL, Small CJ, Batterham RL et al. Peripheral oxyntomodulin reduces food intake and body weight gain in rats. Endocrinology 2004;145: 2687-2695.
26. Parkinson JR, Chaudhri OB, Kuo YT et al. Differential patterns of neuronal activation in the brainstem and hypothalamus following peripheral injection of GLP-1, oxyntomodulin and lithium chloride in mice detected by manganese-enhanced magnetic resonance imaging (MEMRI). Neuroimage 2009;44:1022-1031.
27. Chaudhri OB, Parkinson JR, Kuo YT et al. Differential hypothalamic neuronal activation following peripheral injection of GLP-1 and oxyntomodulin in mice detected by manganese-enhanced magnetic resonance imaging. Biochem Biophys Res Commun 2006;350:298-306.
28. Gu W, Lloyd DJ, Chinookswong N et al. Pharmacological targeting of glucagon and glucagon-like peptide 1 receptors has different effects on energy state and glucose homeostasis in diet-induced obese mice. J Pharmacol Exp Ther 2011;338:70-81.
29. Mu J, Jiang G, Brady E et al. Chronic treatment with a glucagon receptor antagonist lowers glucose and moderately raises circulating glucagon and glucagon-like peptide 1 without severe alpha cell hypertrophy in dietinduced obese mice. Diabetologia 2011;54:2381-2391.
30. Engel SSXL, Andryuk PJ, Davies MJ, Amatruda J, Kaufman K, Goldstein BJ. Efficacy and tolerability of MK-0893, a glucagon receptor antagonist (GRA), in patients with type 2 diabetes (T2DM). Diabetes 2011;(Suppl 1): A85.
31. Ali S, Lamont BJ, Charron MJ, Drucker DJ. Dual elimination of the glucagon and GLP-1 receptors in mice reveals plasticity in the incretin axis. J Clin Invest 2011;121:1917-1929.