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Response of Hepatic Mitochondrial -Glycerophosphate Dehydrogenase and Malic Enzyme to 3,5,3'- Triiodothyronine in Streptozotocin-Diabetic Rats^*

Departamento de Endocrinologia Experimental, Institute de Inuestigaciones Biomedicas del C.S.I.C, Facultad de Medicina, Universidad Autonoma de Madrid Madrid 28029, Spain

Address correspondence and requests for reprints to: Dr. T. Jolin, Instituto de Investigaciones Biomedicas del CSIC, Facultad de Medicina, Universidad Autonoma de Madrid, Madrid 28029, Spain.

Abstract

Hepatic mitochondrial -glycerophosphate dehydrogenase (-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 (K_a). 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 K_a 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 a-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 -GPD and ME to T₃ injection in FR rats was comparable to that of C groups. The a-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 6688% 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 a-GPD and ME to T₃ in D rats suggest that cellular factors play a role in inhibiting orincreasing the response to a given concentration of the T₃-receptor complex. (Endocrinology 123: 248–257,1988)

Footnotes

^* This work was supported by grants from Comision Asesora de Investigation Cientifica y Tenica (661/426) and from Fondo de Investigaciones Sanitarias de la Seguridad Social (86/701).

Received July 16, 1987.