• Sandra Bonhomme, Ana Guijarro, Stefan Keslacy, Carolina G Goncalves, Susumu Suzuki, Chung Chen, and Michael M Meguid.
• Surgical Metabolism and Nutrition Laboratory, Neuroscience Program, Department of Surgery, University Hospital, SUNY Upstate Medical University, Syracuse, New York, USA; Laboratory of Biological Nutrition EA2498, University Paris-Descartes, Faculty of Pharmacy, Paris, France.
• Nutrition. 2011 Jan 1; 27 (1): 73-80.

ObjectiveIn the severely obese, Roux-en-Y gastric bypass (RYGB) reverses diabetes before body weight loss occurs. We determined changes in protein expression of insulin receptor (IR), its substrates (IRS1 and IRS2), and their phosphorylated state (p-IR and p-IRS1/2) in skeletal muscle (SM), liver and adipose tissue (AT), and GLUT4 in SM and AT, 14 and 28 d after RYGB to gaining insight into the time-related dynamics of insulin transduction pathway that may contribute to diabetes resolution.BackgroundRYGB induces a rapid weight loss followed by a slower weight loss period, leading to reversal of diabetes. We hypothesize that diabetes reversal is due to RYGB-induced up-regulation of insulin signaling pathway.MethodsDiet-induced obese rats had RYGB or sham-operation (obese-controls). Daily food intake, body weight, glucose, insulin, and adiponectin were measured. IR, IRS1, IRS2, p-IR, and p-IRS1/2 were measured in SM, liver, and AT and GLUT4 in SM and AT, 14 and 28 d after RYGB, respectively, reflecting the rapid and slower weight loss periods after RYGB.ResultsOn day 14, in RYGB rats versus obese-controls, food intake, body weight, and fat mass decreased. Rats became normo-glycemic and had low insulin levels and elevated glucose:insulin ratio and decreased adiponectin concentrations. This persisted to day 28, except that adiponectin rose. No change in IR occurred on day 14, in RYGB rats versus obese-controls. By day 28 RYGB rats had a higher IR expression in SM and liver, but no changes in AT. RYGB induced a time-related increase in p-IR in liver and in pIRS1/2 in SM and liver. An increase in GLUT4 occurred by day 28 in SM and AT.ConclusionsImprovement in diabetes occurred after RYGB due to up-regulation in key insulin pathway proteins at several levels, predominantly in SM and liver in association with ongoing caloric restriction, body weight, and fat mass loss.Copyright © 2011 Elsevier Inc. All rights reserved.

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