Hepatic glucose cycling does not contribute to the development of hyperglycemia in Zucker diabetic fatty rats

Hepatic glucose cycling, whereby glucose is taken up by the liver, partiall y metabolized, then recycled to glucose, makes a substantial contribution t o the development of hyperglycemia in IDDM. This stimulation of glucose cyc ling appears to be associated with elevated rates of fatty acid oxidation, Whether hepatic glucose cycling also contributes to the development of hype rglycemia in NIDDM is unclear. Using a model of NIDDM, the Zucker diabetic fatty (ZDF) rat, rye determined whether glucose cycling was enhanced. Hepat ocytes from ZDF rats exhibited higher rates of glucose phosphorylation and glycolysis, but there was no increase in the rate of cycling between glucos e and glucose-6-phosphate or between glycolytically derived pyruvate and gl ucose. Despite the increased rates of glycolysis, the production of CO2 in liver cells from ZDF rats was no different, from rates measured in cells fr om control animals. Instead, there was a large increase in the accumulation of lactate and pyruvate in the ZDF liver cells. The addition of 2-bromopal mitate, an inhibitor of fatty acid oxidation that inhibited glucose cycling in hepatocytes from IDDM rats, had no effect on glucose cycling in cells f rom ZDF rats. We therefore conclude that, unlike in IDDM, hepatic glucose c ycling does not contribute to the development of hyperglycemia in the NIDDM Zucker rat.