Age-related differences in the response of hepatic microsomal glucose-6-phosphatase to triiodothyronine and triamcinolone in the rat.

A previous report from this laboratory demonstrated age-related differences in the hormonal regulation of hepatic glucose-6-phosphatase (G-6-Pase). A detailed kinetic analysis of G-6-Pase activity has been performed to distinguish between effects on the microsomal carrier for glucose-6-phosphate and those on the enzyme itself. The maximum velocity (Vmax) was determined in untreated microsomes and microsomes treated with sodium deoxycholate (DOC); the Vmax of the enzyme (VE) was equal to the Vmax in the presence of DOC, and the Vmax of the carrier (VT) was calculated from the Vmax of untreated microsomes and the latency (the activity of DOC-treated microsomes not expressed by the intact preparation). The age-related decrease in G-6-Pase activity was caused by a decrease in the VE. In 3-month-old rats, the VE was increased 2,5-fold by treatment with T3, whereas triamcinolone or the two hormones in combination caused little effect; in 24-month-old animals, the VE was increased 10-fold by T3 and 2-fold by either triamcinolone or the two hormones in combination. In contrast, in 3-month-old animals, the VT was increased 2-fold by triamcinolone, 1.5-fold by T3, and 2-fold by the two hormones in combination; in 24-month-old animals, the VT was increased 3.5-fold by triamcinolone, was not affected by T3, and was increased 1.5-fold by the two hormones in combination. These differences could not be explained by changes in the response of isolated microsomes to sodium deoxycholate or by effects on the energy of activation of G-6-Pase. The results provide detailed evidence for an altered response to either T3 or triamcinolone in hepatocytes from old animals.