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, 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.
Henly
D C
DC
Department of Biochemistry, University of Queensland, Brisbane, Australia. henly@biosci.uq.edu.au
Chauvet
M C
MC
Phillips
J W
JW
D000818:Animals; D003920:Diabetes Mellitus / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D005227:Fatty Acids / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D006943:Hyperglycemia / Q000209:etiology*; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D009765:Obesity; D010084:Oxidation-Reduction / Q000187:drug effects; D010168:Palmitates / Q000494:pharmacology; D051381:Rats; D011924:Rats, Zucker / Q000502:physiology*; D012016:Reference Values
D005227:Fatty Acids; D010168:Palmitates; C022776:2-bromopalmitate; D005947:Glucose