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Journal of Clinical Endocrinology & Metabolism , doi:10.1210/jc.2008-1030
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The Journal of Clinical Endocrinology & Metabolism Vol. 93, No. 12 4656-4663
Copyright © 2008 by The Endocrine Society

Mechanism for Improved Insulin Sensitivity after Gastric Bypass Surgery

Benjamin T. Bikman, Donghai Zheng, Walter J. Pories, William Chapman, John R. Pender, Rita C. Bowden, Melissa A. Reed, Ronald N. Cortright, Edward B. Tapscott, Joseph A. Houmard, Charles J. Tanner, Jihyun Lee and G. Lynis Dohm

The Metabolic Institute for the Study of Diabetes and Obesity (B.T.B., D.Z., W.J.P., R.C.B., M.A.R., R.N.C., J.A.H., C.J.T., G.L.D.), and the Departments of Exercise and Sport Science (B.T.B., D.Z., M.A.R., R.N.C., J.A.H., C.J.T.), Surgery (W.J.P., W.C., J.R.P., R.C.B.), and Physiology (R.N.C., E.B.T., G.L.D.), East Carolina University, Greenville, North Carolina 27834; and Department of Endocrinology-Metabolism (J.L.), School of Medicine, Catholic University, Daegu, 705-718, Republic of Korea

Address all correspondence and requests for reprints to: G. Lynis Dohm, Ph.D., Department of Physiology, Brody School of Medicine, East Carolina University, 6N98 600 Moye Boulevard, Greenville, North Carolina 27834. E-mail: dohmg{at}ecu.edu.

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 {approx} 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 {kappa}B{alpha} was higher in the postsurgery vs. the morbidly obese and weight-matched controls, indicating reduced inhibitor of {kappa}B 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 {kappa}B kinase β activity and enhanced insulin signaling in muscle.







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Copyright © 2008 by The Endocrine Society