Iodothyronine deiodination in the brain of diabetic rats: influence of thyroid status.
Experimental diabetes causes profound alterations in the metabolism of thyroxine (T4), including a decrease in hepatic triiodothyronine (T3) generation from T4 via 5'-deiodination (5'-D). Because 5'-D in brain differs markedly from that in liver, both in enzymatic mechanism and in the response to hypothyroidism, we studied iodothyronine deiodination, in particular T4 to T3 conversion (T4-T3), by incubating 125I T4 with particulate fractions of cerebral cortex (Cx) and cerebellum (Cm) from rats made diabetic by injection of streptozotocin. In nondiabetic thyroidectomized (Tx) rats Cx and Cm T4-T3 activity was increased approximately ten-fold and two-fold, respectively, compared with intact controls. Diabetic Tx rats did not differ from nondiabetic Tx rats in the rate of net T3 production from T4 but the formation of 3,3'-T2 was slightly reduced. Insulin-treated diabetic-Tx rats showed a pattern of T4 metabolism in Cx and Cm virtually identical to that of nondiabetic Tx rats. The rate of T3 degradation, determined in parallel incubations of Cx and Cm with 125I T3, did not differ significantly among the groups, indicating that the observed differences in net T3 production were due to changes in T4 5'-D activity. Intact diabetic rats compared to nondiabetic controls showed no significant changes in T4-T3 either in Cx or in Cm. Administration of T3, 0.8 microgram per 100 g bw per day for 6 days, by constant infusion to intact rats raised T4-T3 in Cx and Cm to levels found in Tx rats. Treatment of intact diabetics with T3 caused qualitatively similar changes, i.e., a hypothyroid response.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D001835:Body Weight; D002531:Cerebellum / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000188:drug therapy / Q000378:metabolism*; D007037:Hypothyroidism / Q000150:complications / Q000378:metabolism*; D007328:Insulin / Q000627:therapeutic use; D007453:Iodide Peroxidase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008297:Male; D011441:Propylthiouracil / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013974:Thyroxine / Q000378:metabolism*; D014284:Triiodothyronine / Q000096:biosynthesis*
D007328:Insulin; D014284:Triiodothyronine; D011441:Propylthiouracil; D007453:Iodide Peroxidase; D013974:Thyroxine