title: Enhanced glucose metabolism in cultured human skeletal muscle after Roux-en-Y gastric bypass surgery.
abstract: BACKGROUND
  Roux-en-Y gastric bypass (RYGB) surgery rapidly increases whole body insulin sensitivity, with changes in several organs including skeletal muscle. Objectives were to determine whether improvements in insulin action in skeletal muscle may occur directly at the level of the myocyte or secondarily from changes in systemic factors associated with weight loss. Myotubes were derived before and after RYGB surgery. The setting was Karolinska University Hospital and Karolinska Institutet, Stockholm, Sweden.
  
  
  METHODS
  Eight patients (body mass index (BMI) 41.8 kg/m(2); age 41 yr) underwent RYGB surgery. Before and 6 months after RYGB surgery, skeletal muscle biopsies were collected from vastus lateralis muscle. Satellite cells derived from skeletal muscle biopsies were propagated in vitro as myoblasts and differentiated into myotubes.
  
  
  RESULTS
  Expression of myogenic markers is increased in myoblasts derived from biopsies taken 6 months after bypass surgery, compared with their respective presurgery condition. Furthermore, glycogen synthesis, tyrosine phosphorylation of insulin receptor (IRS)-1-Tyr612 and Interleukin (IL)-8 secretion were increased, while fatty acid oxidation and circulating IL8 levels remain unaltered. Myotubes derived from muscle biopsies obtained after RYGB surgery displayed increased insulin-stimulated phosphorylation of protein kinase B (PKB)-Thr308 and proline-rich Akt substrate of 40 kDa (PRAS40)-Thr246.
  
  
  CONCLUSIONS
  RYGB surgery is accompanied by enhanced glucose metabolism and insulin signaling, altered IL8 secretion and changes in mRNA levels and myogenic markers in cultured skeletal muscle cells. Thus, RYGB surgery involves intrinsic reprogramming of skeletal muscle to increase peripheral insulin sensitivity and glucose metabolism.
authors: Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden; These authors contributed equally to this work.
authors: Emmani B M
authors: EB
authors: Nascimento
authors: Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; These authors contributed equally to this work.
authors: Isabelle
authors: I
authors: Riedl
authors: Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
authors: Lake Qunfeng
authors: LQ
authors: Jiang
authors: Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
authors: Sameer S
authors: SS
authors: Kulkarni
authors: Division of Surgery, Department of Clinical Sciences, Karolinska Institutet, Danderyds Hospital, Stockholm, Sweden.
authors: Erik
authors: E
authors: Näslund
authors: Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden; Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden. Electronic address: anna.krook@ki.se.
authors: Anna
authors: A
authors: Krook
mesh_terms: D000328:Adult; D001706:Biopsy; D002478:Cells, Cultured; D005260:Female; D015390:Gastric Bypass / Q000379:methods*; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D010535:Laparoscopy; D050356:Lipid Metabolism; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology; D009767:Obesity, Morbid / Q000378:metabolism / Q000473:pathology / Q000601:surgery*
chemical_list: D005947:Glucose
keywords: Circulating factors; Glucose metabolism; Lipid metabolism; Roux-en-Y gastric bypass surgery; Skeletal muscle