title: Evaluating the mechanisms of improved glucose homeostasis after bariatric surgery in Ossabaw miniature swine.
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 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.
authors.affiliation: Department of Surgery, University of Washington, Seattle, WA 98195, USA.
authors.forename: Jonathan G
authors.initials: JG
authors.lastname: Sham
authors.affiliation: Department of Surgery, University of Washington, Seattle, WA 98195, USA.
authors.forename: Vlad V
authors.initials: VV
authors.lastname: Simianu
authors.affiliation: Department of Surgery, University of Washington, Seattle, WA 98195, USA.
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Wright
authors.affiliation: Department of Surgery, University of Washington, Seattle, WA 98195, USA.
authors.forename: Skye D
authors.initials: SD
authors.lastname: Stewart
authors.affiliation: Department of Cellular and Integrative Physiology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
authors.forename: Mouhamad
authors.initials: M
authors.lastname: Alloosh
authors.affiliation: Department of Cellular and Integrative Physiology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Sturek
authors.affiliation: Department of Medicine, University of Washington, Seattle, WA 98195, USA.
authors.forename: David E
authors.initials: DE
authors.lastname: Cummings
authors.affiliation: Department of Surgery, University of Washington, Seattle, WA 98195, USA ; Department of Health Services, University of Washington, Seattle, WA 98195, USA.
authors.forename: David R
authors.initials: DR
authors.lastname: Flum
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism*; D003920:Diabetes Mellitus / Q000097:blood / Q000209:etiology* / Q000503:physiopathology; D004195:Disease Models, Animal; D004386:Duodenum / Q000601:surgery*; D005260:Female; D015390:Gastric Bypass; D005951:Glucose Tolerance Test; D006706:Homeostasis; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D009765:Obesity / Q000097:blood / Q000150:complications / Q000601:surgery*; D013552:Swine; D013556:Swine, Miniature; D013997:Time Factors; D015431:Weight Loss
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D007328:Insulin