title: Gastric bypass up-regulates insulin signaling pathway.
abstract: OBJECTIVE
  In 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.
  
  
  BACKGROUND
  RYGB 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.
  
  
  METHODS
  Diet-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.
  
  
  RESULTS
  On 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.
  
  
  CONCLUSIONS
  Improvement 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.
authors.affiliation: 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.
authors.forename: Sandra
authors.initials: S
authors.lastname: Bonhomme
authors.affiliation: Surgical Metabolism and Nutrition Laboratory, Neuroscience Program, Department of Surgery, University Hospital, SUNY Upstate Medical University, Syracuse, New York, USA.
authors.forename: Ana
authors.initials: A
authors.lastname: Guijarro
authors.affiliation: Surgical Metabolism and Nutrition Laboratory, Neuroscience Program, Department of Surgery, University Hospital, SUNY Upstate Medical University, Syracuse, New York, USA; Department of Exercise Science, Syracuse University, Syracuse, New York, USA.
authors.forename: Stefan
authors.initials: S
authors.lastname: Keslacy
authors.affiliation: Surgical Metabolism and Nutrition Laboratory, Neuroscience Program, Department of Surgery, University Hospital, SUNY Upstate Medical University, Syracuse, New York, USA; Department of Surgery, Positivo University, Curitiba, PR, Brazil.
authors.forename: Carolina G
authors.initials: CG
authors.lastname: Goncalves
authors.affiliation: Surgical Metabolism and Nutrition Laboratory, Neuroscience Program, Department of Surgery, University Hospital, SUNY Upstate Medical University, Syracuse, New York, USA.
authors.forename: Susumu
authors.initials: S
authors.lastname: Suzuki
authors.affiliation: Department of Statistics, Management Information and Decision, Whitman School of Management, Syracuse University, Syracuse, New York, USA.
authors.forename: Chung
authors.initials: C
authors.lastname: Chen
authors.affiliation: Surgical Metabolism and Nutrition Laboratory, Neuroscience Program, Department of Surgery, University Hospital, SUNY Upstate Medical University, Syracuse, New York, USA. Electronic address: meguidm@upstate.edu.
authors.forename: Michael M
authors.initials: MM
authors.lastname: Meguid
mesh_terms: D052242:Adiponectin / Q000097:blood; D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D015992:Body Mass Index; D003920:Diabetes Mellitus / Q000378:metabolism* / Q000628:therapy; D004195:Disease Models, Animal; D002149:Energy Intake; D015390:Gastric Bypass; D051275:Glucose Transporter Type 4 / Q000097:blood; D007328:Insulin / Q000097:blood*; D055504:Insulin Receptor Substrate Proteins / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism; D009765:Obesity / Q000378:metabolism / Q000601:surgery*; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D011972:Receptor, Insulin / Q000378:metabolism*; D015398:Signal Transduction; D015854:Up-Regulation; D015431:Weight Loss
chemical_list: D052242:Adiponectin; D001786:Blood Glucose; D051275:Glucose Transporter Type 4; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; D011972:Receptor, Insulin