Gastric bypass surgery enhances glucagon-like peptide 1-stimulated postprandial insulin secretion in humans

Abstract

Objective: 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.

Research design and methods: 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.

Results: 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.

Conclusions: 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.

FIG. 1.

Blood glucose (C), insulin (B), and insulin secretion rate (A) in response to liquid meal ingestion at screening visit of Asym-GB (n = 12, solid line, closed symbols) vs. Hypo-GB (n = 11, dashed line, open symbols). Data are shown for the number of subjects at any given time as means ± SEM (only 2 of 11 subjects from Hypo-GB group completed the study).

FIG. 2.

Blood glucose levels and insulin response during oral-IV hyperglycemic clamp with Ex-9 (dashed line, open symbols) or saline infusion (solid line, closed symbols) in Asym-GB (left), Hypo-GB (middle), and nonsurgical control subjects (right). Blood glucose (A), insulin (B), and insulin secretion rates (C) are shown. Data are presented as means ± SEM.

FIG. 3.

Glucagon (A), GLP-1 (B), and GIP (C) response to meal ingestion during hyperglycemic clamp with and without Ex-9 infusion (saline: solid line, Ex-9: dashed line) in the three study groups. Data are presented as means ± SEM.