Growth hormone (GH) can oppose the catabolic effects of glucocorticoids. However, both hormones have adverse effects on carbohydrate metabolism. Here we examined the interactive effects of GH and the glucocorticoid methylprednisolone (MP) on glucose tolerance, insulin resistance and [3H]2,6-deoxyglucose uptake of peripheral tissues in rats. Female Wistar rats received either saline, GH (2.7 mg/kg), MP (5.0 mg/kg) or 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 anesthetized and injected with human insulin (0.5 U/kg), [3H]2,6-deoxyglucose (500 microCi/kg), and [14C]mannitol (25 microCi/kg), to estimate insulin resistance and [3H]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 back to normal when GH was given in combination with MP. After a glucose tolerance test no significant differences in glucose area under the curve were detected when comparing individual groups with the control group, but samples 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 alone had no effect (122+/-19, P<0.3). After an i.v. bolus of insulin the group receiving GH+MP had a significantly (P<0.007) higher level of circulating glucose compared with controls (6.5+/-0.3 mM vs 4.4+/-0.7 mM). Despite this, there were no differences in peripheral glucose uptake between the 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 resistance.
T Johansen, M Deckert, T Mandrup-Poulsen, and K Malmlof
J I Reimers, A K Rasmussen, A E Karlsen, U Bjerre, H Liang, O Morin, H U Andersen, T Mandrup-Poulsen, A G Burger, U Feldt-Rasmussen, and J Nerup
Interleukin-1β has been implicated as a pathogenic factor in the development of autoimmune thyroiditis. When given for 5 days to normal non-diabetes-prone Wistar Kyoto rats, it decreased plasma concentrations of total tri-iodothyronine and thyroxine and increased plasma TSH. These effects were not prevented by co-injection of nitroarginine methyl ester or aminoguanidine, inhibitors of NO synthases. Exposure to interleukin-1β dose-dependently reduced iodine uptake in FRTL-5 cells, but had no effect on thyroglobulin secretion. Nitrite was not detected in the FRTL-5 cell culture media after exposure to interleukin-1β. However, reverse transcription PCR analysis of mRNA isolated from interleukin-1β-exposed FRTL-5 cells revealed a transitory expression of the inducible NO synthase, which was markedly lower than inducible NO synthase induction in interleukin-1β-exposed isolated rat islets of Langerhans. Co-incubation with the NO synthase inhibitor N G-monomethylarginine did not ameliorate the effect of interleukin-1β on FRTL-5 cell iodine uptake. Furthermore, we demonstrate that daily injections of interleukin-1β for 13 weeks aggravated spontaneous thyroiditis and induced severe hypothyroidism in non-diabetic diabetes-prone BB rats. The data suggest that NO does not mediate interleukin-1β-induced inhibition of rat thyroid function in vivo or in vitro in FRTL-5 cells, and the induction of hypothyroidism by interleukin-1β in diabetes-prone BB rats is speculated to be due to exacerbation of recruitment and activation of intrathyroidal mononuclear cells.
Journal of Endocrinology (1996) 151, 147–157