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 and abdominal subcutaneous adipose tissue biopsies were taken before and at the end of each clamp. The mRNA levels of insulin receptor, p85 alpha-phosphatidylinositol-3 kinase (p85 alpha PI-3K), insulin dependent glucose transporter (Glut4), hexokinase II, glycogen synthase, lipoprotein lipase (LPL) in muscle and in adipose tissue, hormone sensitive lipase and peroxisome proliferator-activated receptor gamma (PPAR gamma) in adipose tissue were quantified 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 during the hyperinsulinemic clamp (74+/-9 vs 85+/-5 micromol/kg free fat mass/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 amol/microg total RNA, P<0.05) and in adipose tissue (2490+/-260 vs 4860+/-880 amol/microg total RNA, P<0.05), but did not change the expression of the other mRNAs. We conclude from this study that GH therapy did not alter whole body insulin sensitivity and the response of gene expression to insulin in skeletal muscle of adult GHD patients, but it did increase LPL expression in muscle and adipose tissue. This result could be related to the documented beneficial effect of GH therapy on lipid metabolism.
Khalfallah
Y
Y
INSERM U.449, René Laennec Faculty of Medicine, Lyon, France.
Sassolas
G
G
Borson-Chazot
F
F
Vega
N
N
Vidal
H
H
D000236:Adenoma / Q000150:complications / Q000378:metabolism; D000273:Adipose Tissue / Q000378:metabolism*; D000328:Adult; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D051275:Glucose Transporter Type 4; D006006:Glycogen Synthase / Q000235:genetics; D013006:Growth Hormone / Q000172:deficiency*; D006593:Hexokinase / Q000235:genetics; D019382:Human Growth Hormone / Q000627:therapeutic use; D006801:Humans; D007328:Insulin / Q000502:physiology*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008071:Lipoprotein Lipase / Q000235:genetics; D008297:Male; D009004:Monosaccharide Transport Proteins / Q000235:genetics; D009124:Muscle Proteins; D018482:Muscle, Skeletal / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D010911:Pituitary Neoplasms / Q000150:complications / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D011972:Receptor, Insulin / Q000235:genetics; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics; D018709:Statistics, Nonparametric; D014157:Transcription Factors / Q000235:genetics
D051275:Glucose Transporter Type 4; D007328:Insulin; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; C495692:SLC2A4 protein, human; D014157:Transcription Factors; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D006006:Glycogen Synthase; D019869:Phosphatidylinositol 3-Kinases; D006593:Hexokinase; D011972:Receptor, Insulin; D008071:Lipoprotein Lipase