Mechanism for improved insulin sensitivity after gastric bypass surgery

J Clin Endocrinol Metab. 2008 Dec;93(12):4656-63. doi: 10.1210/jc.2008-1030. Epub 2008 Sep 2.


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/m(2); n = 93]; 2) weight-matched (BMI = 25 to 35 kg/m(2); n = 310); 3) morbidly obese (BMI > 35 kg/m(2); n = 43); and 4) postsurgery patients (BMI approximately 30 kg/m(2); 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-pSer(312) in the postsurgery group was lower than morbidly obese and weight-matched groups. Inhibitor kappaBalpha was higher in the postsurgery vs. the morbidly obese and weight-matched controls, indicating reduced inhibitor of kappaB kinase beta 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 kappaB kinase beta activity and enhanced insulin signaling in muscle.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Abdominal Muscles / metabolism
  • Abdominal Muscles / pathology
  • Adult
  • Blood Glucose / metabolism
  • Body Mass Index
  • Female
  • Gastric Bypass*
  • Glucose / metabolism
  • Glucose Tolerance Test
  • Humans
  • I-kappa B Proteins / genetics
  • I-kappa B Proteins / metabolism
  • Insulin Receptor Substrate Proteins / genetics
  • Insulin Receptor Substrate Proteins / metabolism
  • Insulin Resistance / physiology*
  • Muscle, Skeletal / physiology
  • Obesity / therapy


  • Blood Glucose
  • I-kappa B Proteins
  • IRS1 protein, human
  • Insulin Receptor Substrate Proteins
  • Glucose