RESPONSE OF HEPATIC PROTEINS TO 3,5,3'-TRI-IODO-L-THYRONINE IN DIABETIC RATS

In order to study whether peripheral action of thyroid hormones is alt ered in insulin deficiency and to elucidate the biological consequence s of alteration of the cytosolic 3,5,3'-tri-iodo-L-thyronine (T-3) bin ding protein (CTBP), we measured malic enzyme, T-3-responsive nuclear n protein, CTBP and nuclear thyroid hormone receptor in the liver and kidney of streptozotocin (STZ)-induced diabetic rats that were treated with or without insulin and/or a receptor-saturating dose of T-3. The following results were obtained. 1. Induction of malic enzyme by T-3 was apparently diminished in diabetic rats. However, supplementary inj ection of insulin enabled previously given Tg to take effect in diabet ic rats. 2. T-3-responsiveness of other hepatic proteins (n protein an d CTBP) was not altered by insulin in diabetic rats. 3. The level of n protein was increased by insulin in diabetic rats in vivo and in perf used rat liver, indicating that the hepatic n protein is a novel insul in-responsive protein. T-3 and insulin increased the level of n protei n non-synergistically in diabetic rat liver. 4. Hepatic nuclear recept or levels were not altered in diabetic rats. 5. Hepatic CTBP levels we re decreased in diabetic rats. This was not due to the toxic effect of STZ. Low CTBP level was only partially increased by insulin after 30 days of diabetic period. Renal CTBP levels were not altered in diabeti c rats with or without insulin treatment. These results indicate that reduction of CTBP did not influence the hepatic response to a receptor -saturating dose of T-3, although CTBP may regulate the nuclear T-3 tr ansport, and that fundamental action of a receptor-saturating dose of T-3 was not attenuated in diabetic rat liver.