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- W2077224737 abstract "The present study has assessed the potential involvement of hexokinase in the control of insulin-mediated glucose metabolism in insulin-sensitive and -resistant skeletal muscle. Soleus muscle strips from lean (insulin-sensitive) and obese (insulin-resistant) Zucker rats were incubated with 10 or 10,000 microU insulin.ml-1 and then homogenized using a protocol to maintain the location of hexokinase in situ. Hexokinase is inhibited by glucose 6-phosphate, a metabolic intermediate which may have a central role in the regulation of glycogen synthesis. Two separate measurements of hexokinase activity were made on each muscle homogenate: the total hexokinase activity (glucose 6-phosphate was metabolized immediately by glucose 6-phosphate dehydrogenase) and the fractional hexokinase activity (glucose 6-phosphate accumulated so as to regulate the enzyme as in vivo). The total hexokinase activity was equal in insulin-sensitive and -resistant muscle and was unaffected by the extracellular insulin concentration. The fractional hexokinase activity was significantly increased by insulin (10,000 microU.ml-1) in all muscles (lean, 82%; obese, 52%; P < 0.05) although the stimulated fractional hexokinase activity was lower in the muscle from obese Zucker rats compared to lean (P < 0.05). These results provide evidence that insulin decreases the inhibition of hexokinase by glucose 6-phosphate in insulin-sensitive but not in insulin-resistant muscle. This study has revealed short-term regulation of hexokinase by insulin which is defective in insulin-resistant skeletal muscle. Thus, the study has identified hexokinase as a potential regulatory site of insulin action that is abnormal in insulin resistance. The altered regulation of hexokinase may be a major contributing factor to the reduced insulin-mediated glucose fluxes in insulin-resistant skeletal muscle." @default.
- W2077224737 created "2016-06-24" @default.
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- W2077224737 date "1996-10-01" @default.
- W2077224737 modified "2023-09-25" @default.
- W2077224737 title "Abnormal Regulation of Hexokinase in Insulin-Resistant Skeletal Muscle" @default.
- W2077224737 doi "https://doi.org/10.1006/bmme.1996.0069" @default.
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