Gavin L A, Cavalieri R R
J Endocrinol Invest. 1986 Apr;9(2):127-33. doi: 10.1007/BF03348082.
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)
实验性糖尿病会导致甲状腺素（T4）代谢发生深刻变化，包括肝脏通过5'-脱碘作用（5'-D）从T4生成三碘甲状腺原氨酸（T3）的过程减少。由于脑内的5'-D在酶促机制和对甲状腺功能减退的反应方面与肝脏中的显著不同，我们通过将125I T4与注射链脲佐菌素致糖尿病大鼠的大脑皮质（Cx）和小脑（Cm）的微粒体部分一起孵育，研究了碘甲状腺原氨酸脱碘作用，特别是T4向T3的转化（T4-T3）。与完整对照组相比，在非糖尿病甲状腺切除（Tx）大鼠中，Cx和Cm的T4-T3活性分别增加了约10倍和2倍。糖尿病Tx大鼠从T4产生净T3的速率与非糖尿病Tx大鼠没有差异，但3,3'-T2的形成略有减少。胰岛素治疗的糖尿病Tx大鼠在Cx和Cm中的T4代谢模式与非糖尿病Tx大鼠几乎相同。在Cx和Cm与125I T3的平行孵育中测定的T3降解速率在各组之间没有显著差异，表明观察到的净T3产生差异是由于T4 5'-D活性的变化。与非糖尿病对照组相比，完整的糖尿病大鼠在Cx或Cm中的T4-T3没有显著变化。对完整大鼠每天以每100 g体重0.8微克的剂量持续输注T3，共6天，可使Cx和Cm中的T4-T3升高到Tx大鼠中的水平。用T3治疗完整的糖尿病大鼠会引起定性相似的变化，即甲状腺功能减退反应。（摘要截短于250字）
