title: Exaggerated glucagon-like peptide 1 response is important for improved β-cell function and glucose tolerance after Roux-en-Y gastric bypass in patients with type 2 diabetes.
abstract: β-Cell function improves in patients with type 2 diabetes in response to an oral glucose stimulus after Roux-en-Y gastric bypass (RYGB) surgery. This has been linked to the exaggerated secretion of glucagon-like peptide 1 (GLP-1), but causality has not been established. The aim of this study was to investigate the role of GLP-1 in improving β-cell function and glucose tolerance and regulating glucagon release after RYGB using exendin(9-39) (Ex-9), a GLP-1 receptor (GLP-1R)-specific antagonist. Nine patients with type 2 diabetes were examined before and 1 week and 3 months after surgery. Each visit consisted of two experimental days, allowing a meal test with randomized infusion of saline or Ex-9. After RYGB, glucose tolerance improved, β-cell glucose sensitivity (β-GS) doubled, the GLP-1 response greatly increased, and glucagon secretion was augmented. GLP-1R blockade did not affect β-cell function or meal-induced glucagon release before the operation but did impair glucose tolerance. After RYGB, β-GS decreased to preoperative levels, glucagon secretion increased, and glucose tolerance was impaired by Ex-9 infusion. Thus, the exaggerated effect of GLP-1 after RYGB is of major importance for the improvement in β-cell function, control of glucagon release, and glucose tolerance in patients with type 2 diabetes.
authors: Department of Endocrinology, Hvidovre Hospital, Hvidovre, Denmark. nils.bruun.joergensen@regionh.dk
authors: Nils B
authors: NB
authors: Jørgensen
authors: Carsten
authors: C
authors: Dirksen
authors: Kirstine N
authors: KN
authors: Bojsen-Møller
authors: Siv H
authors: SH
authors: Jacobsen
authors: Dorte
authors: D
authors: Worm
authors: Dorte L
authors: DL
authors: Hansen
authors: Viggo B
authors: VB
authors: Kristiansen
authors: Lars
authors: L
authors: Naver
authors: Sten
authors: S
authors: Madsbad
authors: Jens J
authors: JJ
authors: Holst
mesh_terms: D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D005215:Fasting / Q000097:blood; D005260:Female; D015390:Gastric Bypass; D005746:Gastric Emptying / Q000187:drug effects; D005749:Gastric Inhibitory Polypeptide; D005934:Glucagon / Q000378:metabolism; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism*; D000067757:Glucagon-Like Peptide-1 Receptor; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000494:pharmacology; D018027:Receptors, Glucagon / Q000037:antagonists & inhibitors
chemical_list: D001786:Blood Glucose; C000593833:GLP1R protein, human; D000067757:Glucagon-Like Peptide-1 Receptor; D010446:Peptide Fragments; D018027:Receptors, Glucagon; C083773:exendin (9-39); D005749:Gastric Inhibitory Polypeptide; D052216:Glucagon-Like Peptide 1; D005934:Glucagon
references: Diabetes. 2012 Sep;61(9):2349-58
references: 22721966
references: J Clin Endocrinol Metab. 2011 Jan;96(1):229-36
references: 21047924
references: Diabetes. 2011 Sep;60(9):2308-14
references: 21868791
references: Am J Physiol Endocrinol Metab. 2012 Jul 1;303(1):E122-31
references: 22535748
references: J Clin Endocrinol Metab. 2011 Sep;96(9):E1372-9
references: 21778221
references: J Clin Endocrinol Metab. 2011 Jul;96(7):2227-35
references: 21543426
references: Diabetes. 1993 Nov;42(11):1678-82
references: 8405712
references: J Clin Endocrinol Metab. 1983 Jun;56(6):1306-12
references: 6341393
references: Neurogastroenterol Motil. 2013 Apr;25(4):346-e255
references: 23360316
references: Int J Obes Relat Metab Disord. 2001 Aug;25(8):1206-14
references: 11477506
references: Regul Pept. 1984 Sep;9(1-2):35-46
references: 6505290
references: Comput Methods Programs Biomed. 1996 Aug;50(3):253-64
references: 8894385
references: Diabetes. 1999 Jan;48(1):86-93
references: 9892226
references: Am J Clin Nutr. 2012 Mar;95(3):609-13
references: 22318758
references: Diabetologia. 2009 Feb;52(2):199-207
references: 19037628
references: J Clin Endocrinol Metab. 2011 Aug;96(8):2525-31
references: 21593117
references: Obes Surg. 2012 Jul;22(7):1084-96
references: 22359255
references: Am J Physiol Endocrinol Metab. 2010 Nov;299(5):E706-12
references: 20716694
references: Scand J Clin Lab Invest. 2012 Sep;72(5):410-9
references: 22708619
references: J Clin Endocrinol Metab. 2008 Jul;93(7):2479-85
references: 18430778
references: Diabet Med. 2013 Mar;30(3):267-75
references: 23075228
references: Diabetes. 1992 Feb;41(2):241-53
references: 1733816
references: Obes Surg. 2011 Jul;21(7):896-901
references: 21559794
references: Diabetes Care. 2007 Jul;30(7):1709-16
references: 17416796
references: Diabetes. 2010 Jun;59(6):1330-7
references: 20215429
references: Diabetes. 1993 Nov;42(11):1663-72
references: 8405710
references: Int J Obes (Lond). 2010 Mar;34(3):462-71
references: 20029383
references: Diabetes. 2001 Jun;50(6):1363-70
references: 11375337
references: Diabetologia. 2012 Jul;55(7):1890-901
references: 22538359
references: Diabetes Obes Metab. 2013 Mar;15(3):258-63
references: 23039360
references: Ann Surg. 1995 Sep;222(3):339-50; discussion 350-2
references: 7677463
references: Diabetes. 1994 Apr;43(4):535-9
references: 8138058
references: Obes Surg. 1999 Jun;9(3):223-8
references: 10484306
references: J Clin Endocrinol Metab. 1985 Nov;61(5):917-25
references: 4044780
references: Diabetologia. 2011 Oct;54(10):2506-14
references: 21656330
references: Physiol Rev. 2007 Oct;87(4):1409-39
references: 17928588
references: Endocrinology. 1998 Nov;139(11):4448-54
references: 9794451
references: J Endocrinol. 2002 Feb;172(2):355-62
references: 11834453
references: J Biol Chem. 1991 Feb 15;266(5):2897-902
references: 1704369
references: Diabetes Care. 2012 Jan;35(1):137-42
references: 22040841
references: Diabetes Care. 1996 Sep;19(9):1018-30
references: 8875104
references: J Clin Invest. 1998 Apr 1;101(7):1421-30
references: 9525985
references: Diabetes. 2005 Mar;54(3):603-8
references: 15734833
references: Obes Surg. 1998 Jun;8(3):253-60
references: 9678192
references: Obes Surg. 2006 Dec;16(12):1594-601
references: 17217635
references: Diabetes. 2011 May;60(5):1599-607
references: 21441444
references: Diabetologia. 2011 Aug;54(8):2093-102
references: 21614570
references: Diabetes. 1992 Mar;41(3):368-77
references: 1551497
references: Diabetes Care. 2010 Jul;33(7):1438-42
references: 20368410
references: J Clin Invest. 1989 Nov;84(5):1620-8
references: 2681272
references: Ann Surg. 2003 Oct;238(4):467-84; discussion 84-5
references: 14530719
references: N Engl J Med. 2012 Apr 26;366(17):1577-85
references: 22449317