Effects of inhibin on activin A-Induced glucose metabolism in rat hepatocytes.

This study was conducted to investigate the effects of inhibin on hepatic glucose metabolism. We have previously reported that activin A induced a dose-dependent glycogenolytic action on hepatocytes, and that 10(-9) M activin A induced a maximum glycogenolytic effect. Inhibin itself induced no increase or decrease in glucose output at any dose tested. At a concentration of 10(-10) M, inhibin was seen to inhibit 10(-9) M activin A-induced glucose output by 30% as compared to the control. In contrast to its inhibitory effect on the action of activin A, 10(-10) M and higher concentrations of inhibin did not inhibit angiotensin II-or vasopressin-induced glycogenolysis. We further investigated the mechanism of the inhibitory effect of inhibin on activin A-induced glycogenolysis, and found that 10(-10) M inhibin did inhibit the increase in cytoplasmic-free calcium concentration that was seen with 10(-9) M activin A.We also investigated the effects of inhibin on the activin A-induced production of inositol trisphosphates, and the results showed that 10(-10) M inhibin inhibited the activin A-induced production of inositol trisphosphates by 30% compared to the control. Furthermore, it was demonstrated that inhibin did not affect the binding of activin A to isolated hepatocytes. These data demonstrated that inhibin inhibited the activin A-induced glycogenolysis by inhibiting the increases of inositol trisphosphates and cytoplasmic free calcium concentrations.