Hepatic
glucose cycling, whereby
glucose is taken up by the liver, partially metabolized, then recycled to
glucose, makes a substantial contribution to the development of
hyperglycemia in
IDDM. This stimulation of
glucose cycling appears to be associated with elevated rates of
fatty acid oxidation. Whether hepatic
glucose cycling also contributes to the development of
hyperglycemia in
NIDDM is unclear. Using a model of
NIDDM, the Zucker diabetic fatty (ZDF) rat, we determined whether
glucose cycling was enhanced. Hepatocytes from ZDF rats exhibited higher rates of
glucose phosphorylation and glycolysis, but there was no increase in the rate of cycling between
glucose and
glucose-6-phosphate or between glycolytically derived
pyruvate and
glucose. Despite the increased rates of glycolysis, the production of CO2 in liver cells from ZDF rats was no different from rates measured in cells from control animals. Instead, there was a large increase in the accumulation of
lactate and
pyruvate in the ZDF liver cells. The addition of
2-bromopalmitate, an inhibitor of
fatty acid oxidation that inhibited
glucose cycling in hepatocytes from
IDDM rats, had no effect on
glucose cycling in cells from ZDF rats. We therefore conclude that, unlike in
IDDM, hepatic
glucose cycling does not contribute to the development of
hyperglycemia in the
NIDDM Zucker rat.