Mechanism for improved insulin sensitivity after gastric bypass surgery

BT Bikman, D Zheng, WJ Pories… - The Journal of …, 2008 - academic.oup.com
BT Bikman, D Zheng, WJ Pories, W Chapman, JR Pender, RC Bowden, MA Reed
The Journal of Clinical Endocrinology & Metabolism, 2008academic.oup.com
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 …
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 κBα was higher in the postsurgery vs. the morbidly obese and weight-matched controls, indicating reduced inhibitor of κB kinase β 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 κB kinase β activity and enhanced insulin signaling in muscle.
Oxford University Press