Response of hepatic mitochondrial alpha-glycerophosphate dehydrogenase and malic enzyme to 3,5,3'-triiodothyronine in streptozotocin-diabetic rats.

Hepatic mitochondrial alpha-glycerophosphate dehydrogenase (alpha-GPD) and cytosolic malic enzyme (ME) response to a single injection of a receptor-saturating dose of T3 were measured 10, 20, and 30 days after diabetes induction, and compared with values in controls either fed ad libitum (C) or under a restricted diet (FR). An insulin-treated diabetic (D + I) group was also included. Basal enzyme levels as well as enzyme response to T3 injection were correlated with nuclear T3 content, maximal nuclear T3-binding capacity (MBC) and equilibrium association constant (Ka). Diabetes for 10, 20, and 30 days was associated with a progressive decrease in the MBC; the mean decrease was 17%, 50%, and 59%, respectively, from the corresponding C values. The MBC in FR animals did not change appreciably during the experimental period. Moreover, neither the decreased MBC in D groups nor MBC in C, FR, or D + I animals were influenced by T3 injection. The Ka values were comparable in all experimental groups. Specifically bound nuclear T3 was decreased within the experimental period between 33% and 73% in D rats and 6% and 39% in FR rats respect to C values. T3 injection raised the mean nuclear T3 content in all groups. However, at each time interval the mean values of the nuclear T3 in D groups was significantly lower than that in C, FR, or D + I groups after T3 injection. The basal alpha-GPD activity tended to be relatively stable during the experimental period in both D and FR rats, whereas ME activity in D and FR groups was decreased, respectively, 52-64% and 18-39% from C values. The response of both alpha-GPD and ME to T3 injection in FR rats was comparable to that of C groups. The alpha-GPD response to T3 in D rats was not different from that of C rats on days 10 and 20 of the experiment, but on day 30 it decreased by 26%. In contrast, the induction of ME by T3 was severely decreased (by 66-88% of C values) within the experimental diabetes period. Thus, the measurements made in FR rats excluded the possibility that the quantitative changes in the enzyme response to T3 in D rats were nutrition-dependent. The differences between the response of alpha-GPD and ME to T3 in D rats suggest that cellular factors play a role in inhibiting or increasing the response to a given concentration of the T3-receptor complex.