Skeletal muscle glucose transporter gene expression is not affected by injecting growth-hormone-secreting cells in young rats

Abstract

To elucidate the diabetogenic effect of growth hormone on glucose metabolism the regulation of glucose transporter (GLUT) gene expression was examined in rat skeletal muscles. Female Wistar-Furth rats were implanted subcutaneously with growth-hormone-producing pituitary tumour (GH3) cells. Animals were killed 4 or 9 weeks after GH3 cell injection. Although body weight, serum growth hormone and insulin-like growth factor I levels were remarkably elevated during the 4-9 week Period, serum blood glucose levels were within normal range. Muscles were obtained from the quadriceps muscle, diaphragm and heart, respectively. Northern blot analysis and Western blot analysis were performed using specific cDNA probes and antibodies. During the 4-9 week period, the levels of muscle GLUT 1 and 4 mRNA (corrected by fl-actin mRNA level) in each muscle from the rats injected with turnout cells were not significantly different from those of control rats. Chronic elevation of growth hormone in these rats did not cause any change in GLUT 1 and 4 expression compared to the controls during the euglycaemic period. These results provide the first evidence that chronic growth hormone elevation itself does not affect a key gene of in vivo glucose metabolism.

Chronic growth hormone treatment in normal rats reduces post-prandial skeletal muscle plasma membrane GLUT1 content, but not glucose transport or GLUT4 expression and localization

“…Likewise, muscle GLUT4 mRNA content was similar in the control and in the hGH-treated group. These results, which confirm the work of others [5,7], indicate that hGH treatment did not change whole muscle content of GLUT4 protein or mRNA levels. In the same muscle, a 22 % decrease in GLUT1 mRNA content was detected (Table 2).…”

“…Although this reduction did not reach statistical significance (P 0.08 with one-tail t test), it suggests that hGH may decrease muscle GLUT1 mRNA. A previous paper has shown no change in muscle GLUT1 mRNA content in rats bearing a GH-secreting tumour [7], possibly because the GH plasma level was much lower than in the current study.…”

“…Glucose transport across the plasma membrane in skeletal muscle tissue is regulated by two glucose transporters : GLUT4 and GLUT1. Although skeletal muscle glucose transport has been reported to be reduced after GH treatment [5,6], no changes were found [5,7] in the total content of GLUT4 or GLUT1 proteins in this tissue. Since the whole muscle content of GLUT4 or GLUT1 may not correlate with the number of functional transporters localized to the plasma membrane, a second goal of this study was to determine whether GH treatment results in a specific decrease in the number of plasma membrane glucose transporters.…”

“…However, chronic GH treatment induces a compensatory increase in the plasma insulin concentration [5][6][7]. Therefore, it is possible that skeletal muscle glucose transport after GH treatment would be normal if measured under in i o conditions.…”

The Metabolic Actions of Growth Hormone

“…The decrease in glucose uptake by rat skeletal muscle is not accompanied by a decrease in the abundance or activity of the insulin-sensitive glucose transporter, GLUT4 (133, 396,586). In fact, 12 h after a single injection of GH, the rate of transport of the nonmetabolizable analogue, 3-0-methylglucose was increased in soleus mus-cle (156), although continued treatment with GH for 10 days decreased glucose transport in response to insulin.…”