ABSTRACT
The isolated effect of growth hormone on carbohydrate metabolism in rat skeletal muscle was studied in growth hormone-deficient dwarf rats (dw/dw) treated with either recombinant human growth hormone or saline for 10 days. In addition, age-matched heterozygous (DW/dw) (normal weight and plasma IGF-I) control rats were treated with saline. Growth hormone increased weight gain from 0.1+/-0.1 (s.e.m) to 3.6+/-0.1 g/day and plasma IGF-I concentration from 364+/-23 to 451+/-32 ng/ml. Glucose metabolism in skeletal muscle perfused with basal, submaximal and maximal concentrations (0, 600 and 60 000 pmol/l respectively) of insulin was not changed by growth hormone. No change could be detected in the total number of glucose transporters (GLUT1 and GLUT4) in the skeletal muscles, except from a lower amount of GLUT4 in the soleus muscle in the heterozygous control group. However, at submaximal insulin concentrations, skeletal muscle glucose uptake and transport were significantly lower in the heterozygous control group compared with the growth hormone-deficient group. This could indicate either a direct long-term effect of growth hormone or more likely a secondary effect attributable to the difference in body weight (205.2+/-3.1 vs 361. 6+/-5.9 g for dwarf rats and heterozygous controls respectively), and thereby muscle fibre size, between the groups probably resulting in lower average interstitial insulin and glucose concentrations at a given plasma concentration in the heterozygous rats. It is concluded that restoration of subnormal growth hormone concentrations for 10 days has no effect on insulin-stimulated glucose metabolism in skeletal muscle in vitro.
Subject(s)
Glucose/metabolism , Growth Disorders/drug therapy , Growth Hormone/deficiency , Human Growth Hormone/therapeutic use , Insulin/metabolism , Muscle Proteins , Muscle, Skeletal/metabolism , Analysis of Variance , Animals , Biological Transport/drug effects , Culture Techniques , Glucose Transporter Type 1 , Glucose Transporter Type 4 , Growth Disorders/metabolism , Heterozygote , Male , Monosaccharide Transport Proteins/metabolism , Muscle, Skeletal/drug effects , Postprandial Period , Rats , Rats, Mutant StrainsABSTRACT
The effect of recombinant human growth hormone (rhGH) on growth and composition of muscle was studied in growth hormone-deficient rats (dw/dw) treated for 10 days with either rhGH (GH) or with placebo (PLA). Age-matched control rats (DW/dw) (AGE) were treated as PLA. Growth rate increased (P < 0.05) when rats were treated with rhGH and plasma insulin-like growth factor-1 concentration was higher (P < 0.05) in GH and AGE than in PLA. The wet weight of the soleus (SOL) and the extensor digitorum longus muscles (EDL) was less in PLA compared to GH and AGE (P < 0.05). In the SOL, the amount of myosin heavy chain (MHC) I was lower (69.1 +/- 1.7%) (Mean +/- SEM) in PLA compared to both GH (85.3 +/- 2.3%) and AGE (76.4 +/- 1.6%) (P < 0.05). At the same time the amount of MHC IIA/IIX was higher (30.9 +/- 2.2%) in PLA compared to GH (14.7 +/- 2.3%) and AGE (23.6 +/- 1.6% (P < 0.05)). In EDL, treatment with rhGH did not significantly affect MHC-isoforms or the fibre type composition, but 11% more MHC IIB and 11% less MHC IIA/IIX was observed in PLA compared to AGE (P < 0.05) suggesting a long-term effect of growth hormone. MHC-isoform data were confirmed using histochemistry. In addition, in the SOL, the maximal activity of 3-hydroxyacyl-CoA dehydrogenase (HAD) in GH and AGE was higher (22 and 27%, respectively) than in PLA (P < 0.05). In the EDL, no differences were observed in maximal activity of HAD. In conclusion, the data support a role for growth hormone in muscle fibre growth and differentiation.
Subject(s)
Dwarfism/drug therapy , Growth Hormone/deficiency , Growth Hormone/pharmacology , Muscle Fibers, Skeletal/cytology , Muscle Fibers, Skeletal/drug effects , Age Factors , Animals , Cell Differentiation/drug effects , Cell Differentiation/physiology , Dwarfism/metabolism , Heterozygote , Insulin-Like Growth Factor I/genetics , Insulin-Like Growth Factor I/metabolism , Male , Muscle Fibers, Skeletal/chemistry , Muscle, Skeletal/chemistry , Muscle, Skeletal/cytology , Myosin Heavy Chains/analysis , Rats , Rats, Mutant StrainsABSTRACT
We have investigated whether hypoxia and muscle contractions stimulate glucose transport in perfused rat muscle to the same extent, additively and with the same sensitivity to the microbial products calphostin C and wortmannin. Hindlimb glucose uptake increased gradually from 3.4+/-0.5 to a maximal level of 12.7+/-0.6 micromol g-1 h-1 (n=11) after 50 min of hypoxia. Compared with hypoxia, the effect of maximal electrical stimulation of the sciatic nerve on muscle glucose uptake was more than two-fold higher (27+/-2 micromol g-1 h-1 (n=14)). This was due to a higher contraction- vs. hypoxia-induced glucose transport rate in oxidative fibers. The stimulatory effect of hypoxia and electrical stimulation was not additive. Contraction-induced muscle glucose transport was inhibitable by both calphostin C and wortmannin in the micromolar range, whereas the effect of hypoxia was totally insensitive to these drugs. Our data suggest that diacylglycerol/phorbol ester-sensitive protein kinase C is involved in stimulation of muscle glucose transport by contractions and that in contrast to the prevailing concept, hypoxia and contractions do not stimulate muscle glucose transport by the same signaling mechanism.
