title: Effect of growth hormone treatment on insulin action in adipocytes from children with Prader-Willi syndrome.
abstract: OBJECTIVE
  To study the effect of growth hormone (GH) treatment (2-4 months) on insulin action in adipocytes isolated from children with Prader-Willi syndrome (PWS), in whom GH deficiency appears to be a primary defect. We investigated the complex effects of GH on carbohydrate metabolism, as part of a current clinical trial of GH treatment in children with PWS.
  
  
  METHODS
  Biopsies of subcutaneous abdominal adipose tissue were obtained from 12 children with PWS before and after 2-4 months of GH treatment. Lipogenesis was determined by the incorporation of radiolabelled glucose into lipids in isolated adipocytes, and glycerol release to the incubation medium was used as an index of lipolysis. GLUT4 RNA was measured by solution hybridization.
  
  
  RESULTS
  With low glucose concentrations, at which glucose transport is rate-limiting, maximal insulin-induced lipogenesis was increased by 120% after GH treatment (P < 0.05), but the sensitivity to insulin (half-maximum effective hormone concentration) was unchanged. This was not accompanied by a significant change in the RNA expression of GLUT4. Neither responsiveness (maximum effect) nor sensitivity of insulin-induced inhibition of lipolysis was affected by GH treatment.
  
  
  CONCLUSIONS
  GH treatment of children with PWS results in an upregulation of insulin-induced lipogenesis in isolated adipocytes, with no effect on insulin-induced inhibition of lipolysis. The data suggest that the site of the effect of GH on lipogenesis is distal to the insulin hormone-receptor interaction, but does not involve altered GLUT4 expression.
authors.affiliation: Department of Pediatrics, Huddinge Hospital, Sweden.
authors.forename: A
authors.initials: A
authors.lastname: Kamel
authors.forename: S
authors.initials: S
authors.lastname: Norgren
authors.forename: A C
authors.initials: AC
authors.lastname: Lindgren
authors.forename: H
authors.initials: H
authors.lastname: Luthman
authors.forename: P
authors.initials: P
authors.lastname: Arner
authors.forename: C
authors.initials: C
authors.lastname: Marcus
mesh_terms: D017667:Adipocytes / Q000187:drug effects*; D002648:Child; D002675:Child, Preschool; D051275:Glucose Transporter Type 4; D019382:Human Growth Hormone / Q000172:deficiency / Q000627:therapeutic use*; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000627:therapeutic use*; D008066:Lipolysis / Q000187:drug effects; D009004:Monosaccharide Transport Proteins / Q000235:genetics; D009124:Muscle Proteins; D011218:Prader-Willi Syndrome / Q000188:drug therapy*; D012333:RNA, Messenger / Q000096:biosynthesis; D015854:Up-Regulation
chemical_list: D051275:Glucose Transporter Type 4; D007004:Hypoglycemic Agents; D007328:Insulin; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; D012333:RNA, Messenger; C495692:SLC2A4 protein, human; D019382:Human Growth Hormone