Removal of duodenum elicits GLP-1 secretion

Abstract

Objective: To evaluate the effect of removal of the duodenum on the complex interplay between incretins, insulin, and glucagon in nondiabetic subjects.

Research design and methods: For evaluation of hormonal secretion and insulin sensitivity, 10 overweight patients without type 2 diabetes (age 61 ± 19.3 years and BMI 27.9 ± 5.3 kg/m(2)) underwent a mixed-meal test and a hyperinsulinemic-euglycemic clamp before and after pylorus-preserving pancreatoduodenectomy for ampulloma.

Results: All patients experienced a reduction in insulin (P = 0.002), C-peptide (P = 0.0002), and gastric inhibitory peptide (GIP) secretion (P = 0.0004), while both fasting and postprandial glucose levels increased (P = 0.0001); GLP-1 and glucagon responses to the mixed meal increased significantly after surgery (P = 0.02 and 0.031). While changes in GIP levels did not correlate with insulin, glucagon, and glucose levels, the increase in GLP-1 secretion was inversely related to the postsurgery decrease in insulin secretion (R(2) = 0.56; P = 0.012) but not to the increased glucagon secretion, which correlated inversely with the reduction of insulin (R(2) = 0.46; P = 0.03) and C-peptide (R(2) = 0.37; P = 0.04). Given that the remaining pancreas presumably has preserved intraislet anatomy, insulin secretory capacity, and α- and β-cell interplay, our data suggest that the increased glucagon secretion is related to decreased systemic insulin.

Conclusions: Pylorus-preserving pancreatoduodenectomy was associated with a decrease in GIP and a remarkable increase in GLP-1 levels, which was not translated into increased insulin secretion. Rather, the hypoinsulinemia may have caused an increase in glucagon secretion.

Figure 1

Surgical and reconstruction procedure: the pancreatic head, the duodenum, the common bile duct, and the gallbladder were removed en bloc, leaving the functioning pylorus at the gastric outlet intact. The continuity of the gastrointestinal apparatus was restored by an end-to-side invaginated pancreaticojejunostomy. Further downstream, an end-to-side hepaticojejunostomy and side-to side gastroenterostomy or an end-to-side pylorus jejunostomy was made. This figure is designed to simplify the understanding of the anatomical changes on which our model is based.

Figure 2

Plasma concentrations of glucose (A), insulin (B), C-peptide (C), GLP-1 (D), glucagon (E), and GIP (F) in patients examined before and after surgery. At t = 0 min, an oral mixed meal was ingested. Data are presented as means ± SEM. P values were calculated using repeated measures by ANOVA. Significant difference (P < 0.05) at individual time points (Bonferroni post hoc test). *Significant (P ≤ 0.05) differences at individual time points. Increased glucose levels (A) are consequent to decreased insulin and C-peptide levels after surgery (B and C). Incretin adaptation (D and F) to removal of duodenum and consequent reduction of GIP (E) are shown. The incretins showed an opposite trend after the surgery, i.e., a major reduction of GIP secretion and increase of GLP-1 release. The rise in glucagon concentration after the removal of duodenum reached the statistical significance after the first hour of the mixed-meal test.