EFFECT OF GROWTH-HORMONE TREATMENT ON INSULIN ACTION IN ADIPOCYTES FROM CHILDREN WITH PRADER-WILLI-SYNDROME

Objective: To study the effect of growth hormone (GH) treatment (2-4 m onths) on insulin action in adipocytes isolated from children with Pra der-Willi syndrome (PWS), in whom GH deficiency appears to be a primar y defect. We investigated the complex effects of GH on carbohydrate me tabolism, as part of a current clinical trial of GH treatment in child ren with PWS. Methods: Biopsies of subcutaneous abdominal adipose tiss ue were obtained from 12 children with PWS before and after 2-4 months of GH treatment. Lipogenesis was determined by the incorporation of r adiolabelled glucose into lipids in isolated adipocytes, and glycerol release to the incubation medium was used as an index of lipolysis, GL UT4 RNA was measured by solution hybridization. Results: With low gluc ose concentrations, at which glucose transport is rate-limiting, maxim al insulin-induced lipogenesis was increased by 120% after GH treatmen t (P < 0.05), but the sensitivity to insulin (half-maximum effective h ormone concentration) was unchanged. This was not accompanied by a sig nificant change in the RNA expression of GLUT4. Neither responsiveness (maximum effect) nor sensitivity of insulin-induced inhibition of lip olysis was affected by GH treatment, Conclusions: GH treatment of chil dren with PWS results in an upregulation of insulin-induced lipogenesi s in isolated adipocytes, with no effect on insulin-induced inhibition of lipolysis. The data suggest that the site of the effect of GH on l ipogenesis is distal to the insulin hormone-receptor interaction, but does not involve altered GLUT4 expression.