The role of growth hormone and glucocorticoid in glucose handling in vivo

Growth hormone (GH) can oppose the catabolic effects of glucocorticoids. Ho wever, both hormones have adverse effects on carbohydrate metabolism. Here we examined the interactive effects of GH and the glucocorticoid methylpred nisolone (MP) on glucose tolerance, insulin resistance and [H-3]2,6-deoxygl ucose uptake of peripheral tissues in rats. Female Wistar rats received either saline, GH (2.7 mg/kg), MP (5.0 mg/kg) o r GH+MP. After 7 days treatment, animals were subjected to an i.v. glucose tolerance test. In a second experiment, animals treated as above were anest hetized and injected with human insulin (0.5 U/kg), [H-3]2,6-deoxyglucose ( 500 mu Ci/kg), and [C-14]mannitol (25 mu Ci/kg), to estimate insulin resist ance and [H-3]2,6 deoxyglucose uptake in fat and muscle. Weight,gain in controls was 7.6 +/- 1.7 g, while GH treatment increased the mean body weight by 18.7 +/- 2.2 g (P<0.0002) and MP inhibited weight gain down to 0.0 +/- 1.0 g (P<0.004). This drop in weight gain was reversed bac k to normal when GH was given in combination with MP. After a glucose toler ance test no significant differences in glucose area under the curve were d etected when comparing individual groups with the control group, but sample s taken just before this test revealed that basal insulin was significantly elevated in the group treated with GH (174 +/- 27 pM, P<0.008), or GH+MP ( 209 +/- 21 pM, P<0.004), when compared with controls (107 +/- 17 pM). MP al one had no effect (122 +/- 19, P<0.3). After an i.v. bolus of insulin the g roup receiving GH+MP had a significantly (P<0.007) higher level of circulat ing glucose compared with controls (6.5 +/- 0.3 mM vs 4.4 +/- 0.7 mM). Desp ite this, there were no differences in peripheral glucose uptake between th e two groups. In conclusion this study shows that a combined administration of GH and MP decreases the potency by which insulin decreases circulating glucose levels , but that peripheral tissues are not primarily involved in this insulin re sistance.