The influence of starvation, diabetic ketoacidosis, ketone bodies and free fatty acids on glucose metabolism in resting skeletal muscle was studied in the isolated perfused rat hindquarter perparation and in intact rats. In the hindquarter preparation, the provision of 1.3 mM oleate, 1 mM octanoate or 2 mM acetoacetate did not alter the uptake of glucose in the presence of insulin. In contrast, glucose uptake in the presence of insulin was significantly depressed in hindquarters of rats with diabetic ketosis. In fed, fasted and diabetic rats the distribution space of glucose in skeletal muscle in vivo ranged between 15 to 20 per cent (extracellular space, 18 to 20 per cent), indicating that transport into the cell and not phosphorylation was rate-limiting for glucose uptake. The administration of glucose and insulin did not increase the glucose distribution space in fed or fasted rats; however, it caused a marked increase in tissue lactate in the fasted group, suggesting inhibition of pyruvate oxidation. The concentrations of hexose monophosphates in skeletal muscle freeze-clamped in vivo were very similar in the three groups, indicating phosphofructokinase was not inhibited in the fasted or diabetic rats. There were also no major differences in the concentrations of citrate, glycerolphosphate, ATP, ADP and AMP: the concentration of acetyl CoA was increased in both forty-eight hour fasted and diabetic rats and free CoA was diminished in the diabetic rats. Tissue glycogen waslower in fasted and diabetic than in fed rats. The data suggest that in resting skeletal muscle there is no inhibition of glucose metabolism by exogenous fatty acids and ketone bodies anaiagous to that which occurs in heart and diaphragm. The rate limiting step in glucose uptake appears to be its transport into the cell which is inhibited in rats with diabetic ketosis. Glucose metabolism at the level of pyruvate dehydrogenase may be inhibited in skeletal muscle during fasting and diabetes as a result of changes in the concentrations of acetyl CoA and CoA.
Glucose Metabolism in Rat Skeletal Muscle at Rest: Effect of Starvation, Diabetes, Ketone Bodies and Free Fatty Acids
Michael N Goodman, Michael Berger, Neil B Ruderman; Glucose Metabolism in Rat Skeletal Muscle at Rest: Effect of Starvation, Diabetes, Ketone Bodies and Free Fatty Acids. Diabetes 1 November 1974; 23 (11): 881–888. https://doi.org/10.2337/diab.23.11.881
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