Stimulation of glucose production by activin-A in isolated rat hepatocytes.
The effect of activin-A on glycogenolysis was studied in isolated rat hepatocytes. Activin-A stimulated glucose output in hepatocytes in a dose-dependent manner. The maximal effect of the glycogenolytic action of activin-A, which was about 50% of the glucagon action, was obtained at 10(-9) M. When 10(-9) M activin-A and 5 x 10(-9) M glucagon were added simultaneously, the actions of these two agents were additive. In contrast, there was no additivity when 10(-9) M activin-A and 10(-8) M angiotensin-II were added. Activin-A did not increase cAMP at any doses tested, but induced a rapid increase in cytoplasmic free calcium concentration. Activin-A increased the cytoplasmic free calcium concentration even in the presence of 1 microM extracellular calcium, suggesting that activin-A caused calcium release from an intracellular calcium pool(s). The internal calcium pool affected by activin-A appeared to be the same as that affected by either angiotensin-II or vasopressin. When [3H] inositol-labeled hepatocytes were incubated with activin-A, radioactivity in the inositol trisphosphate fraction was rapidly increased. These results indicate that activin-A acts on rat hepatocytes and stimulates glycogenolysis by activating the calcium messenger system.
Mine
T
T
Fourth Department of Internal Medicine, University of Tokyo School of Medicine, Japan.
Kojima
I
I
Ogata
E
E
D028341:Activins; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000502:physiology; D002469:Cell Separation; D000242:Cyclic AMP / Q000378:metabolism; D005934:Glucagon / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism*; D007265:Inhibins / Q000494:pharmacology*; D007295:Inositol Phosphates / Q000378:metabolism; D008099:Liver / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D015290:Second Messenger Systems / Q000187:drug effects
D007295:Inositol Phosphates; D028341:Activins; D000804:Angiotensin II; D007265:Inhibins; D005934:Glucagon; D000242:Cyclic AMP; D005947:Glucose; D002118:Calcium