Decreased basal and acute insulin-stimulated effect on the uptake of glucose and amino acid in vitro by thyroid glands from streptozotocin-diabetic rats

RESUMO

Since experimental diabetes in rats and mice is associated with impairment of several aspects of thyroid function, we determined glucose and amino acid uptake in vitro by isolated thyroid glands from normal and streptozotocin-diabetic rats. Adult male Wistar rats weighing 150-200 g were used. Diabetes was induced by intraperitoneal injection streptozotocin (STZ, 65 mg/kg body weight) and after five days only rats with blood glucose levels higher than 250 mg/dl were used. The thyroid glands were preincubated in Krebs-Ringer bicarbonate buffer in the presence or absence of insulin (0.7 nM to 7 muM) for 90 min and then incubated with the same concentration of the hormone or its vehicle plus 0.2 muCi of [l-l4C]-2-deoxy-D-glucose ([l4C]DG) or [l4C] methylaminoisobutyric acid ([l4C]MeAIB) for 15 to 180 min. The uptake of [l4C]DG or [l4C]MeAIB by the thyroid glands of normal rats increased as a function of incubation time, and the presence of insulin (7 muM) induced a significant increase of labelled DG from 3.30 ñ 0.11 to 4.16 ñ O.12 and of labelled MeAIB from 1.79 ñ 0.06 to 3.10 ñ 0.17 tissue/medium ratio (TIM) after 45 min of incubation. The lowest concentration of insulin that increased both [l4C]DG and [l4C]MeAIB transport was 7 nM. Thyroid glands from STZ rats exhibited lower basal values of [l4C]DG (4.03 ñ 0.11 T/M) or [l4C]MeAIB uptake (1.05 ñ 0.05 T/M) than glands from normal rats (4.62 ñ 0.13 and 1.70 ñ 0.O8 T/M, respectively). Insulin produced a stimulatory effect on the transport of both substrates in STZ rats. However, the maximals stimulating concentration of the hormone did not restore[l4C]DG and [l4C)MeAIB uptake to control values (4.89 + O.17 in STZ rats versus 5.44 ñ 0.17 T/M in controls for [l4C]DG, and 1.51 ñ 0.11 in STZ rats versus 2.19 ñ 0.10 T/M in controls for [l4C]MeAIB). These results indicate that insulin exerts a direct action on the thyroid gland, and its absence or reduction affects thyroid metabolism, contributing, at least in part, to the abnormality in thyroid function associated with diabetes mellitus.