SUPPRESSION OF GLYCOLYSIS IS ASSOCIATED WITH AN INCREASE IN GLUCOSE CYCLING IN HEPATOCYTES FROM DIABETIC RATS

Rates of cycling between glucose and glucose 6-phosphhate and between glucose and pyruvate, and the effects of these cycles on glucose metab olism, were compared in hepatocytes isolated from fasted normal or str eptozotocin-induced diabetic rats. In diabetic hepatocytes the rate of glucose phosphorylation was 30% lower than that in normal hepatocytes , and there was a doubling of the rate of glucose/glucose 6-phosphate cycling. In addition, the rate of glycolysis was 60% fewer in diabetic hepatocytes. This inhibition of glycolysis and stimulation of glucose /glucose 6-phosphate cycling appeared to be a consequence of the eleva ted rates of endogenous fatty acid oxidation observed in diabetic hepa tocytes. The proportion of glycolytically derived pyruvate that was re cycled to glucose was more than doubled in hepatocytes from diabetic r ats compared with normal animals. This increase also appeared to be li nked to the high rates of endogenous fatty acid oxidation in diabetic cells. As a consequence of the increased rates of both these cycles, 8 5% of all glucose molecules taken up by diabetic hepatocytes were recy cled to glucose, compared with only 50% in normal hepatocytes. Glucose cycling is therefore likely to make a substantial contribution to the hyperglycemia of diabetes.