Mechanism for Improved Insulin Sensitivity after Gastric Bypass Surgery

Abstract

Context: Surgical treatments of obesity have been shown to induce rapid and prolonged improvements in insulin sensitivity. Objective: The aim of the study was to investigate the effects of gastric bypass surgery and the mechanisms that explain the improvement in insulin sensitivity. Design: We performed a cross-sectional, nonrandomized, controlled study. Setting: This study was conducted jointly between the Departments of Exercise Science and Physiology at East Carolina University in Greenville, North Carolina. Subjects: Subjects were recruited into four groups: 1) lean body mass index (BMI) 25 kg/m2; n 93 ; 2) weight-matched (BMI 25 to 35 kg/m2; n 310); 3) morbidly obese (BMI 35 kg/m2; n 43); and 4) postsurgery patients (BMI 30 kg/m2; n 40). Postsurgery patients were weight stable 1 yr after surgery. Main Outcome Measures: Whole-body insulin sensitivity, muscle glucose transport, and muscle insulin signaling were assessed. Results: Postsurgery subjects had insulin sensitivity index values that were similar to the lean and higher than morbidly obese and weight-matched control subjects. Glucose transport was higher in the postsurgery vs. morbidly obese and weight-matched groups. IRS1-pSer312 in the postsurgery group was lower than morbidly obese and weight-matched groups. Inhibitor B was higher in the postsurgery vs. the morbidly obese and weight-matched controls, indicating reduced inhibitor of B kinase activity. Conclusions: Insulin sensitivity and glucose transport are greater in the postsurgery patients than predicted from the weight-matched group, suggesting that improved insulin sensitivity after bypass is due to something other than, or in addition to, weight loss. Improved insulin sensitivity is related to reduced inhibitor of B kinase activity and enhanced insulin signaling in muscle. Originally published J Clin Endocrinol Metab, Vol. 93, No. 12, Dec 2008