Expression of insulin target genes in skeletal muscle and adipose tissue in adult patients with growth hormone deficiency: effect of one year recombinant human growth hormone therapy

Our aim was to investigate the effects of one year recombinant human growth hormone (rhGH) therapy on the regulation by insulin of gene expression in muscle and adipose tissue in adults with secondary GH deficiency (GHD). Six GHD subjects without upper-body obesity were submitted to a 3-h euglycemic hyperinsulinemic clamp before and after one year of rhGH therapy. Muscle a nd abdominal subcutaneous adipose tissue biopsies were taken before and at the end of each clamp. The mRNA levels of insulin receptor, p85 alpha -phos phatidylinositol-3 kinase (p85 alpha PI-3K), insulin dependent glucose tran sporter (Glut4), hexokinase II, glycogen synthase, lipoprotein lipase (LPL) in muscle and in adipose tissue, hormone sensitive lipase and peroxisome p roliferator-activated receptor gamma (PPAR gamma) in adipose tissue were qu antified by RT-competitive PCR. One year treatment with rhGH (1.25 IU/day) increased plasma IGF-I concentrations (54 +/- 7 vs 154 +/- 11 ng/ml, P<0.01 ) but did not affect insulin-stimulated glucose disposal rate measured duri ng the hyperinsulinemic clamp (74 +/- 9 vs 85 +/- 5 <mu>mol/kg free fat mas s/min). Insulin significantly increased p85 alpha PI-3K, hexokinase II and Glut4 mRNA levels in muscle both before and after rhGH treatment. One year of GH therapy increased LPL mRNA levels in muscle (38 +/- 2 vs 70 +/- 7 amo l/mug total RNA, P<0.05) and in adipose tissue (2490 +/- 260 vs 4860 +/- 88 0 amol/<mu>g total RNA, P<0.05), but did not change the expression of the o ther rnRNAs. We conclude from this study that GH therapy did not alter whol e body insulin sensitivity and the response of gene expression to insulin i n skeletal muscle of adult GHD patients, but it did increase LPL expression in muscle and adipose tissue. This result could be related to the document ed beneficial effect of GH therapy on lipid metabolism.