Giovanna Muscogiuri , MD 1 , Teresa Mezza , MD 1 , Annamaria Prioletta , MD 1 , Gian Pio Sorice , MD 1 , Gennaro Clemente , MD 2 , Gerardo Sarno , MD 2 , Gennaro Nuzzo , MD 2 , Alfredo Pontecorvi , MD, PHD 1 , Jens J. Holst , MD, PHD 3 , Andrea Giaccari , MD, PHD 1
15 May 2013
To evaluate the effect of removal of the duodenum on the complex interplay between incretins, insulin, and glucagon in nondiabetic subjects.
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.
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.