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

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 pro...

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Main Authors: Jonathan G. Sham, Vlad V. Simianu, Andrew S. Wright, Skye D. Stewart, Mouhamad Alloosh, Michael Sturek, David E. Cummings, David R. Flum
Format: Article
Language:English
Published: Wiley 2014-01-01
Series:Journal of Diabetes Research
Online Access:http://dx.doi.org/10.1155/2014/526972
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author Jonathan G. Sham
Vlad V. Simianu
Andrew S. Wright
Skye D. Stewart
Mouhamad Alloosh
Michael Sturek
David E. Cummings
David R. Flum
author_facet Jonathan G. Sham
Vlad V. Simianu
Andrew S. Wright
Skye D. Stewart
Mouhamad Alloosh
Michael Sturek
David E. Cummings
David R. Flum
author_sort Jonathan G. Sham
collection DOAJ
description 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 AUCinsulin/AUCglucose. Conclusions. Similar to humans, Ossabaw swine exhibit both obesity-dependent and obesity-independent IR. RYGB promoted weight loss, IR improvement, and increased AUCinsulin/AUCglucose, compared to the smaller changes following GJ and GJD, suggesting a combination of upper and lower gut mechanisms in improving glucose homeostasis.
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spelling doaj-art-243e9e81bdf5491abf49a0f94e90d05a2025-02-03T06:00:18ZengWileyJournal of Diabetes Research2314-67452314-67532014-01-01201410.1155/2014/526972526972Evaluating the Mechanisms of Improved Glucose Homeostasis after Bariatric Surgery in Ossabaw Miniature SwineJonathan G. Sham0Vlad V. Simianu1Andrew S. Wright2Skye D. Stewart3Mouhamad Alloosh4Michael Sturek5David E. Cummings6David R. Flum7Department of Surgery, University of Washington, Seattle, WA 98195, USADepartment of Surgery, University of Washington, Seattle, WA 98195, USADepartment of Surgery, University of Washington, Seattle, WA 98195, USADepartment of Surgery, University of Washington, Seattle, WA 98195, USADepartment of Cellular and Integrative Physiology, Indiana University School of Medicine, Indianapolis, IN 46202, USADepartment of Cellular and Integrative Physiology, Indiana University School of Medicine, Indianapolis, IN 46202, USADepartment of Medicine, University of Washington, Seattle, WA 98195, USADepartment of Surgery, University of Washington, Seattle, WA 98195, USABackground. 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 AUCinsulin/AUCglucose. Conclusions. Similar to humans, Ossabaw swine exhibit both obesity-dependent and obesity-independent IR. RYGB promoted weight loss, IR improvement, and increased AUCinsulin/AUCglucose, compared to the smaller changes following GJ and GJD, suggesting a combination of upper and lower gut mechanisms in improving glucose homeostasis.http://dx.doi.org/10.1155/2014/526972
spellingShingle Jonathan G. Sham
Vlad V. Simianu
Andrew S. Wright
Skye D. Stewart
Mouhamad Alloosh
Michael Sturek
David E. Cummings
David R. Flum
Evaluating the Mechanisms of Improved Glucose Homeostasis after Bariatric Surgery in Ossabaw Miniature Swine
Journal of Diabetes Research
title Evaluating the Mechanisms of Improved Glucose Homeostasis after Bariatric Surgery in Ossabaw Miniature Swine
title_full Evaluating the Mechanisms of Improved Glucose Homeostasis after Bariatric Surgery in Ossabaw Miniature Swine
title_fullStr Evaluating the Mechanisms of Improved Glucose Homeostasis after Bariatric Surgery in Ossabaw Miniature Swine
title_full_unstemmed Evaluating the Mechanisms of Improved Glucose Homeostasis after Bariatric Surgery in Ossabaw Miniature Swine
title_short Evaluating the Mechanisms of Improved Glucose Homeostasis after Bariatric Surgery in Ossabaw Miniature Swine
title_sort evaluating the mechanisms of improved glucose homeostasis after bariatric surgery in ossabaw miniature swine
url http://dx.doi.org/10.1155/2014/526972
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