title: Action and therapeutic potential of oxyntomodulin.
abstract: Oxyntomodulin (OXM) is a peptide hormone released from the gut in post-prandial state that activates both the glucagon-like peptide-1 receptor (GLP1R) and the glucagon receptor (GCGR) resulting in superior body weight lowering to selective GLP1R agonists. OXM reduces food intake and increases energy expenditure in humans. While activation of the GCGR increases glucose production posing a hyperglycemic risk, the simultaneous activation of the GLP1R counteracts this effect. Acute OXM infusion improves glucose tolerance in T2DM patients making dual agonists of the GCGR and GLP1R new promising treatments for diabetes and obesity with the potential for weight loss and glucose lowering superior to that of GLP1R agonists.
authors.affiliation: Janssen Research and Devolopment, Cardiovascular and Metabolic Disease, 1516 Welsh and McKean Roads, Spring House, PA 19477, USA.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Pocai
keywords: Body weight; GLP-1; Glucagon; Glucose metabolism; Oxyntomodulin
references.citation: Diabetes. 2013 Jul;62(7):2595-604
references.pmid: 23524641
references.citation: Diabetes Care. 2013 Sep;36(9):2559-65
references.pmid: 23645886
references.citation: Biochem Biophys Res Commun. 2006 Nov 17;350(2):298-306
references.pmid: 17007819
references.citation: Peptides. 1981;2 Suppl 2:41-4
references.pmid: 6283496
references.citation: Endocrinology. 2008 Nov;149(11):5670-8
references.pmid: 18669601
references.citation: Diabetes Care. 2013 Jul;36(7):2118-25
references.pmid: 23645885
references.citation: J Clin Endocrinol Metab. 2001 Dec;86(12):5992
references.pmid: 11739476
references.citation: Endocr Rev. 1999 Dec;20(6):876-913
references.pmid: 10605628
references.citation: Am J Physiol. 1987 Aug;253(2 Pt 1):E208-13
references.pmid: 3303968
references.citation: J Hum Hypertens. 2003 Aug;17(8):577-9
references.pmid: 12874616
references.citation: Int J Obes (Lond). 2013 Oct;37(10):1391-8
references.pmid: 23337772
references.citation: Diabetes. 2005 Jul;54(7):2212-8
references.pmid: 15983224
references.citation: Lancet. 2009 Feb 7;373(9662):473-81
references.pmid: 18819705
references.citation: Diabetes Care. 2013 Jul;36(7):2126-32
references.pmid: 23645884
references.citation: J Endocrinol. 2012 Dec;215(3):335-46
references.pmid: 23019069
references.citation: J Clin Invest. 1984 Mar;73(3):785-93
references.pmid: 6142902
references.citation: Endocrinology. 2004 Jun;145(6):2687-95
references.pmid: 15001546
references.citation: Int J Pharm. 2013 Jan 2;440(1):48-62
references.pmid: 22503954
references.citation: Diabetes Care. 2011 Jul;34(7):1463-8
references.pmid: 21593296
references.citation: JAMA. 2007 Jul 11;298(2):194-206
references.pmid: 17622601
references.citation: Nature. 2013 Jul 25;499(7459):444-9
references.pmid: 23863937
references.citation: Diabetes Obes Metab. 2010 Sep;12(9):766-71
references.pmid: 20649628
references.citation: Gastroenterology. 2004 Aug;127(2):546-58
references.pmid: 15300587
references.citation: Am J Physiol Endocrinol Metab. 2008 Jan;294(1):E142-7
references.pmid: 17971509
references.citation: Digestion. 1996 Nov-Dec;57(6):398-405
references.pmid: 8913701
references.citation: J Pharmacol Exp Ther. 2007 Jul;322(1):148-54
references.pmid: 17395766
references.citation: Am J Physiol Gastrointest Liver Physiol. 2013 Jun 15;304(12):G1117-27
references.pmid: 23599045
references.citation: Regul Pept. 2007 Oct 4;143(1-3):64-8
references.pmid: 17434608
references.citation: Am J Physiol Endocrinol Metab. 2012 Jul 15;303(2):E265-71
references.pmid: 22621866
references.citation: Diabetologia. 2009 Oct;52(10):2046-55
references.pmid: 19688338
references.citation: Diabetes. 2010 Dec;59(12):3099-107
references.pmid: 20823098
references.citation: Br J Pharmacol. 2009 Aug;157(8):1340-51
references.pmid: 19681866
references.citation: J Clin Endocrinol Metab. 2011 Mar;96(3):853-60
references.pmid: 21209033
references.citation: J Clin Endocrinol Metab. 2003 Jun;88(6):2719-25
references.pmid: 12788879
references.citation: Endocrinology. 1996 Sep;137(9):3674-80
references.pmid: 8756532
references.citation: Diabetologia. 1993 Aug;36(8):741-4
references.pmid: 8405741
references.citation: Regul Pept. 2000 Sep 25;93(1-3):45-51
references.pmid: 11033052
references.citation: Diabetes. 2012 Nov;61(11):2753-62
references.pmid: 22933116
references.citation: Gut. 1982 Oct;23(10):854-61
references.pmid: 7117905
references.citation: Diabetes. 2013 Jul;62(7):2178-80
references.pmid: 23596147
references.citation: Am J Physiol. 1996 Sep;271(3 Pt 1):G477-82
references.pmid: 8843773
references.citation: Regul Pept. 1988 May;21(1-2):151-66
references.pmid: 2839871
references.citation: Obesity (Silver Spring). 2012 Aug;20(8):1566-71
references.pmid: 22421924
references.citation: Diabetes. 2013 Oct;62(10):e16-7
references.pmid: 24065798
references.citation: Sci Transl Med. 2013 Oct 30;5(209):209ra151
references.pmid: 24174327
references.citation: N Engl J Med. 2013 Oct 3;369(14):1317-26
references.pmid: 23992601
references.citation: Diabet Med. 2009 Mar;26(3):268-78
references.pmid: 19317822
references.citation: Endocrinology. 2012 Jul;153(7):2945-8
references.pmid: 22730282
references.citation: Diabetes. 2008 Dec;57(12):3169-76
references.pmid: 19033403
references.citation: J Clin Endocrinol Metab. 1992 Jun;74(6):1405-9
references.pmid: 1592887
references.citation: J Clin Endocrinol Metab. 1976 Sep;43(3):675-8
references.pmid: 182712
references.citation: Cardiovasc Diabetol. 2010 Jan 28;9:6
references.pmid: 20109208
references.citation: Gastroenterology. 1998 Nov;115(5):1163-71
references.pmid: 9797371
references.citation: Lancet. 2010 Apr 24;375(9724):1447-56
references.pmid: 20417856
references.citation: Biopolymers. 2012;98(5):443-50
references.pmid: 23203689
references.citation: J Clin Endocrinol Metab. 2004 Jun;89(6):2583-9
references.pmid: 15181027
references.citation: Curr Opin Investig Drugs. 2010 Oct;11(10):1151-7
references.pmid: 20872318
references.citation: Diabetes Obes Metab. 2011 May;13(5):418-25
references.pmid: 21251180
references.citation: J Biol Chem. 1948 Sep;175(2):663-74
references.pmid: 18880761
references.citation: Nat Med. 2013 Jun;19(6):766-72
references.pmid: 23685839
references.citation: N Engl J Med. 1968 Jul 4;279(1):12-7
references.pmid: 4872564
references.citation: Endocrinology. 1993 Aug;133(2):631-8
references.pmid: 8102095
references.citation: Diabetes. 2013 May;62(5):1376
references.pmid: 23613555
references.citation: Diabetes. 2013 Oct;62(10):e18
references.pmid: 24065799
references.citation: Am J Gastroenterol. 1978 Sep;70(3):274-81
references.pmid: 362905
references.citation: Am J Physiol Regul Integr Comp Physiol. 2007 Feb;292(2):R962-70
references.pmid: 17038440
references.citation: Drug Discov Today. 2013 Sep;18(17-18):807-17
references.pmid: 23726889
references.citation: Cell Metab. 2013 Sep 3;18(3):333-40
references.pmid: 24011069
references.citation: Regul Pept. 2009 Jan 8;152(1-3):101-7
references.pmid: 18951927
references.citation: Diabetes Care. 2009 Jan;32(1):84-90
references.pmid: 18931095
references.citation: Proc Natl Acad Sci U S A. 1994 Apr 12;91(8):3242-6
references.pmid: 8159732
references.citation: N Engl J Med. 1987 May 28;316(22):1376-83
references.pmid: 3553949
references.citation: J Clin Endocrinol Metab. 2012 Jan;97(1):121-31
references.pmid: 22031513
references.citation: Biochem Pharmacol. 2013 Jun 1;85(11):1655-62
references.pmid: 23518155
references.citation: Endocrinology. 2010 Apr;151(4):1473-86
references.pmid: 20203154
references.citation: Mol Pharmacol. 2012 Mar;81(3):309-18
references.pmid: 22108912
references.citation: Am J Hypertens. 2010 Mar;23(3):334-9
references.pmid: 20019672
references.citation: FEBS Lett. 1982 Sep 6;146(1):79-86
references.pmid: 7140977
references.citation: Diabetes. 2005 Aug;54(8):2390-5
references.pmid: 16046306
references.citation: Eur J Pharmacol. 2008 Jun 10;587(1-3):243-7
references.pmid: 18474367
references.citation: Diabetologia. 2013 Mar;56(3):588-97
references.pmid: 23262585
references.citation: Dig Dis Sci. 1989 Sep;34(9):1411-9
references.pmid: 2670487
references.citation: Int J Obes (Lond). 2010 Dec;34(12):1715-25
references.pmid: 20531351
references.citation: Br Med J. 1979 Nov 17;2(6200):1252-5
references.pmid: 519400
references.citation: Diabetes Res Clin Pract. 2013 Oct;102(1):e1-4
references.pmid: 24008099
references.citation: Scand J Gastroenterol. 1979;14(2):205-7
references.pmid: 432544
references.citation: Am J Physiol Endocrinol Metab. 2002 Dec;283(6):E1173-7
references.pmid: 12388165
references.citation: Am J Physiol. 1997 Dec;273(6):R1965-71
references.pmid: 9435650
references.citation: Diabetes. 2013 Apr;62(4):1131-8
references.pmid: 23248172
references.citation: Nat Rev Endocrinol. 2010 Dec;6(12):689-97
references.pmid: 20957001
references.citation: J Clin Endocrinol Metab. 2004 Jun;89(6):2832-6
references.pmid: 15181065
references.citation: Diabetes. 2009 Oct;58(10):2258-66
references.pmid: 19602537
references.citation: Cell Metab. 2013 May 7;17(5):779-89
references.pmid: 23663741
references.citation: Int J Obes (Lond). 2012 Jun;36(6):843-54
references.pmid: 21844879
references.citation: Int J Obes (Lond). 2006 Dec;30(12):1729-36
references.pmid: 16619056
references.citation: J Clin Endocrinol Metab. 2003 Oct;88(10):4696-701
references.pmid: 14557443
references.citation: Nat Med. 2012 May 04;18(5):668-9
references.pmid: 22561824
references.citation: J Biol Chem. 1973 Jan 25;248(2):697-706
references.pmid: 4684697
references.citation: Diabetes Care. 1998 Nov;21(11):1925-31
references.pmid: 9802745
references.citation: Nat Clin Pract Endocrinol Metab. 2005 Nov;1(1):22-31
references.pmid: 16929363
references.citation: Front Endocrinol (Lausanne). 2012 May 07;3:62
references.pmid: 22649424
references.citation: PLoS One. 2013 Jun 18;8(6):e65763
references.pmid: 23823755
references.citation: Proc Soc Exp Biol Med. 1959 Oct-Dec;102:621-3
references.pmid: 13840405
references.citation: Lancet. 2008 Oct 4;372(9645):1240-50
references.pmid: 18782641
references.citation: Diabetes. 2011 May;60(5):1561-5
references.pmid: 21430088
references.citation: Lancet. 2009 Jul 4;374(9683):39-47
references.pmid: 19515413
references.citation: Curr Opin Pharmacol. 2013 Dec;13(6):983-8
references.pmid: 24161809
references.citation: Endocrinology. 2009 Aug;150(8):3513-20
references.pmid: 19359390
references.citation: Gastroenterology. 2011 Jul;141(1):150-6
references.pmid: 21334333
references.citation: Annu Rev Physiol. 1997;59:257-71
references.pmid: 9074764
references.citation: Am J Physiol Endocrinol Metab. 2004 Apr;286(4):E621-5
references.pmid: 14678954
references.citation: Nat Chem Biol. 2009 Oct;5(10):749-57
references.pmid: 19597507
references.citation: Nat Rev Drug Discov. 2002 Jul;1(7):529-40
references.pmid: 12120259
references.citation: Arch Surg. 1985 Mar;120(3):355-60
references.pmid: 3970671
references.citation: Clin Sci (Lond). 2013 Jan;124(1):17-26
references.pmid: 22963445
references.citation: Am J Physiol Endocrinol Metab. 2000 Jun;278(6):E1010-8
references.pmid: 10827002
references.citation: Diabetologia. 2013 Jun;56(6):1417-24
references.pmid: 23503814
references.citation: Curr Diabetes Rev. 2013 May;9(3):218-27
references.pmid: 23363296
references.citation: Diabetes. 1995 Nov;44(11):1249-58
references.pmid: 7589820
references.citation: Neuroimage. 2009 Feb 1;44(3):1022-31
references.pmid: 18983926
references.citation: J Pharmacol Exp Ther. 1960 May;129:49-55
references.pmid: 13821530
references.citation: J Pept Sci. 2011 Apr;17(4):270-80
references.pmid: 21294225
references.citation: J Mol Med (Berl). 2001 Oct;79(10):574-80
references.pmid: 11692154
references.citation: Diabetologia. 1999 Mar;42(3):326-9
references.pmid: 10096785
references.citation: Curr Opin Clin Nutr Metab Care. 2013 Nov;16(6):619-24
references.pmid: 24100676
references.citation: Endocrinology. 2012 Jul;153(7):3054-65
references.pmid: 22685263
references.citation: Diabetes Care. 2009 Jul;32(7):1224-30
references.pmid: 19289857
references.citation: Endocrinology. 2001 Oct;142(10):4244-50
references.pmid: 11564680
references.citation: Eur J Clin Invest. 1988 Oct;18(5):499-503
references.pmid: 3147901
references.citation: Mol Metab. 2013 May 29;2(3):205-14
references.pmid: 24049735
references.citation: Biosci Rep. 1981 Feb;1(2):151-5
references.pmid: 6271273
references.citation: Expert Opin Investig Drugs. 2012 Jan;21(1):45-57
references.pmid: 22111970
references.citation: Nat Rev Drug Discov. 2008 Apr;7(4):339-57
references.pmid: 18382464
references.citation: Am J Physiol. 1993 Jan;264(1 Pt 2):R116-22
references.pmid: 8430871
references.citation: Diabetes. 1996 Jun;45(6):832-5
references.pmid: 8635662
references.citation: Biochem Pharmacol. 2010 Dec 1;80(11):1727-35
references.pmid: 20735990
references.citation: J Pharmacol Sci. 2012;118(1):65-74
references.pmid: 32092839
references.citation: Pancreas. 2000 May;20(4):348-60
references.pmid: 10824688
references.citation: J Clin Endocrinol Metab. 1983 Sep;57(3):488-95
references.pmid: 6874888
references.citation: Diabetes. 2013 May;62(5):1453-63
references.pmid: 23305646
references.citation: Gastroenterology. 1997 Jun;112(6):1961-70
references.pmid: 9178688
references.citation: J Biol Chem. 2001 Jul 20;276(29):27197-202
references.pmid: 11356850
references.citation: Cell. 2012 Feb 3;148(3):556-67
references.pmid: 22304921
references.citation: Gastroenterol Jpn. 1985 Feb;20(1):28-36
references.pmid: 4018495
references.citation: C R Seances Acad Sci III. 1981 Oct 19;293(6):323-8
references.pmid: 6797684