Gastric Bypass Surgery Enhances Glucagon-Like Peptide 1-Stimulated Postprandial Insulin Secretion in Humans

• Published in: Diabetes (New York, N.Y.) Vol. 60; no. 9; pp. 2308 - 2314
• Main Authors: SALEHI, Marzieh, PRIGEON, Ronald L, D'ALESSIO, David A
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01.09.2011
• Subjects: Adult; Asymptomatic; Biological and medical sciences; Blood Glucose; Carbohydrates; Diabetes; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Female; Gastric Bypass; Gastrointestinal surgery; Glucagon; Glucagon - blood; Glucagon-Like Peptide 1 - blood; Glucagon-Like Peptide 1 - pharmacology; Glucose; Health aspects; Humans; Hypoglycemia; Hypotheses; Insulin; Insulin - blood; Insulin - metabolism; Insulin Secretion; Islet Studies; Male; Medical sciences; Metabolic diseases; Middle Aged; Pancreas - drug effects; Pancreas - metabolism; Peptide hormones; Peptides; Physiological aspects; Plasma; Postprandial Period - physiology; Research design; Risk factors; United States; Endocrinopathy; Human; Stomach; Pancreatic hormone; Digestive system; Postprandial; Secretion; Diabetes mellitus; Insulin; Glucagon like peptide 1; Gastrointestinal hormone; Bypass; Surgery
• ISSN: 0012-1797; 1939-327X
• DOI: 10.2337/db11-0203

Gastric bypass (GB) surgery is associated with postprandial hyperinsulinemia, and this effect is accentuated in postsurgical patients who develop recurrent hypoglycemia. Plasma levels of the incretin glucagon-like peptide 1 (GLP-1) are dramatically increased after GB, suggesting that its action contributes to alteration in postprandial glucose regulation. The aim of this study was to establish the role of GLP-1 on insulin secretion in patients with GB. Twelve asymptomatic individuals with previous GB (Asym-GB), 10 matched healthy nonoperated control subjects, and 12 patients with recurrent hypoglycemia after GB (Hypo-GB) had pre- and postprandial hormone levels and insulin secretion rates (ISR) measured during a hyperglycemic clamp with either GLP-1 receptor blockade with exendin-(9-39) or saline. Blocking the action of GLP-1 suppressed postprandial ISR to a larger extent in Asym-GB individuals versus control subjects (33 ± 4 vs.16 ± 5%; P = 0.04). In Hypo-GB patients, GLP-1 accounted for 43 ± 4% of postprandial ISR, which was not significantly higher than that in Asym-GB subjects (P = 0.20). Glucagon was suppressed similarly by hyperglycemia in all groups but rose significantly after the meal in surgical individuals but remained suppressed in nonsurgical subjects. GLP-1 receptor blockade increased postprandial glucagon in both surgical groups. Increased GLP-1-stimulated insulin secretion contributes significantly to hyperinsulinism in GB subjects. However, the exaggerated effect of GLP-1 on postprandial insulin secretion in surgical subjects is not significantly different in those with and without recurrent hypoglycemia.