title: 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.
  
  
  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.
authors.affiliation: Department of Medicine, Division of Endocrinology, University of Cincinnati, Cincinnati, Ohio, USA. salehim@uc.edu
authors.forename: Marzieh
authors.initials: M
authors.lastname: Salehi
authors.forename: Ronald L
authors.initials: RL
authors.lastname: Prigeon
authors.forename: David A
authors.initials: DA
authors.lastname: D'Alessio
mesh_terms: D000328:Adult; D001786:Blood Glucose; D005260:Female; D015390:Gastric Bypass; D005934:Glucagon / Q000097:blood; D052216:Glucagon-Like Peptide 1 / Q000097:blood / Q000494:pharmacology*; D006801:Humans; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D008297:Male; D008875:Middle Aged; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism*; D019518:Postprandial Period / Q000502:physiology*
chemical_list: D001786:Blood Glucose; D007328:Insulin; D052216:Glucagon-Like Peptide 1; D005934:Glucagon