Removal of Duodenum Elicits GLP-1 Secretion

TY - JOUR

T1 - Removal of Duodenum Elicits GLP-1 Secretion

AU - Muscogiuri, Giovanna

AU - Mezza, Teresa

AU - Prioletta, Annamaria

AU - Sorice, Gian Pio

AU - Clemente, Gennaro

AU - Sarno, Gerardo

AU - Nuzzo, Gennaro

AU - Pontecorvi, Alfredo

AU - Holst, Jens Juul

AU - Giaccari, Andrea

PY - 2013/6

Y1 - 2013/6

N2 - OBJECTIVETo evaluate the effect of removal of the duodenum on the complex interplay between incretins, insulin, and glucagon in nondiabetic subjects.RESEARCH DESIGN AND METHODSFor 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.RESULTSAll 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.CONCLUSIONSPylorus-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.

AB - OBJECTIVETo evaluate the effect of removal of the duodenum on the complex interplay between incretins, insulin, and glucagon in nondiabetic subjects.RESEARCH DESIGN AND METHODSFor 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.RESULTSAll 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.CONCLUSIONSPylorus-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.

U2 - 10.2337/dc12-0811

DO - 10.2337/dc12-0811

M3 - Journal article

C2 - 23393218

SN - 0149-5992

VL - 36

SP - 1641

EP - 1646

JO - Diabetes Care

JF - Diabetes Care

IS - 6

ER -