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Journal of Diabetes Research
Volume 2014, Article ID 526972, 7 pages
http://dx.doi.org/10.1155/2014/526972
Research Article

Evaluating the Mechanisms of Improved Glucose Homeostasis after Bariatric Surgery in Ossabaw Miniature Swine

1Department of Surgery, University of Washington, Seattle, WA 98195, USA
2Department of Cellular and Integrative Physiology, Indiana University School of Medicine, Indianapolis, IN 46202, USA
3Department of Medicine, University of Washington, Seattle, WA 98195, USA
4Department of Health Services, University of Washington, Seattle, WA 98195, USA

Received 6 June 2014; Revised 29 July 2014; Accepted 7 August 2014; Published 24 August 2014

Academic Editor: Masami Shinohara

Copyright © 2014 Jonathan G. Sham et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background. Roux-en-Y gastric bypass (RYGB) is the most common bariatric operation; however, the mechanism underlying the profound weight-independent effects on glucose homeostasis remains unclear. Large animal models of naturally occurring insulin resistance (IR), which have been lacking, would provide opportunities to elucidate such mechanisms. Ossabaw miniature swine naturally exhibit many features that may be useful in evaluating the anti diabetic effects of bariatric surgery. Methods. Glucose homeostasis was studied in 53 Ossabaw swine. Thirty-two received an obesogenic diet and were randomized to RYGB, gastrojejunostomy (GJ), gastrojejunostomy with duodenal exclusion (GJD), or Sham operations. Intravenous glucose tolerance tests and standardized meal tolerance tests were performed prior to, 1, 2, and 8 weeks after surgery and at a single time-point for regular diet control pigs. Results. High-calorie-fed Ossabaws weighed more and had greater IR than regular diet controls, though only 70% developed IR. All operations caused weight-loss-independent improvement in IR, though only in pigs with high baseline IR. Only RYGB induced weight loss and decreased IR in the majority of pigs, as well as increasing /. Conclusions. Similar to humans, Ossabaw swine exhibit both obesity-dependent and obesity-independent IR. RYGB promoted weight loss, IR improvement, and increased /, compared to the smaller changes following GJ and GJD, suggesting a combination of upper and lower gut mechanisms in improving glucose homeostasis.