The mechanism of decreased insulin sensitivity in glycogen supercompensated muscles

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Muscle insulin sensitivity to glucose uptake is decreased after acute bout of glycogen-depleting exercise. Increased muscle insulin sensitivity after exercise leads to rapid glycogen synthesis in the muscles recruited during exercise, if enough carbohydrate is available for these muscles. Although muscles vigorously take up blood glucose to re-synthesize glycogen for several hours after exercise, insulin-stimulated glucose uptake is decreased in glycogen supercompensated muscles. We tried to examine the mechanism of insulin resistance in glycogen supercompensated muscles.When rats were refed carbohydrate after glycogen-depleting exercise for 4,8, and 16 h, the time course of the decrease in insulin responsiveness of glucose uptake in rat muscles occurred concomitantly with a decrease in insulin- stimulated activation of protein kinase B/Akt. This result strongly suggests that the decreased insulin responsiveness of glucose uptake in glycogen supercompensated muscles is the result of th … More e impairement of PKB/Akt signaling. In our study, impairement of PKB/Akt signaling in glycogen supercompensated muscles was also not due to a increase in the abundance of phosphoinositide phosphatase, SHIP2,SKIP, or PTEN protein.Some previous studies suggested the posibiity that activation of ACC causes the accumulation of lipid intermediates, e.g. diacylglycerol and ceramide, which is involved in the insulin resistance. Our previous study also provided evidence that synthesis of a protein mediates insulin resistance in glycogen supercompensated muscles. In our present study, the abundance of Acetyl CoA Carboxylase (ACC) was increased in glycogen supercompensated muscles, suggesting that increased ACC protein expression might be responsible for insulin resistance in glycogen supercompensated muscles.Furthermore, in our present study, the decrease in insulin responsiveness of glucose uptake and increase in G0/G1 switch protein mRNA expression occurred concurrently during carbohydrate refeeding after exercise. Increased G0/G1 switch protein expression could be involved in the insulin resistance in glycogen supercompensated muscles. Less