NITRIC-OXIDE INHIBITS GLYCOGEN-SYNTHESIS IN ISOLATED RAT HEPATOCYTES

There is increasing evidence for the existence of intrahepatic regulat ion of glucose metabolism by Kupffer cell products. Nitric oxide (NO) is known to inhibit gluconeogenic flux through pyruvate carboxylase an d phosphoenolpyruvate carboxykinase. However, NO may also influence gl ucose metabolism at other levels. Using hepatocytes from fasted rats i ncubated with the NO-donor S-nitroso-N-acetylpenicillamine, we have no w found that the synthesis of glycogen from glucose is even more sensi tive to inhibition by NO than gluconeogenesis. Inhibition of glycogen production by NO was accompanied by a rise in intracellular glucose 6- phosphate and UDPglucose. Activity of glycogen synthase, as measured i n extracts of hepatocytes after the cells had been exposed to NO, was decreased. Experiments with gel-filtered liver extracts revealed that inhibition of glycogen synthase was caused by an inhibitory effect of NO on the conversion of glycogen synthase 6 into glycogen synthase a.