Effects of non-esterified fatty acid availability on insulin stimulated glucose utilisation and tissue pyruvate dehydrogenase activity in the rat

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Abstract
Fatty acids in cardiac muscle compete with glucose for oxidation, thereby inhibiting glucose utilisation. It is not clear whether a similar mechanism is important in resting skeletal muscle. We used the hyperinsulinaemic euglycaemic clamp technique in conscious rats fasted for 20 h to examine the effects of increased plasma non-esterified fatty acid levels (∼1 mmol/l) on glucose metabolism. Insulin was infused at 75 mU/h (plasma insulin, 2.27±0.21 μg/l) or 300mU/h (16.41±0.47 μg/l). An increase in non-esterified fatty acid levels decreased clamp glucose requirement and 3−3H-glucose turnover by 35% (ppp<0.002). The findings are consistent with an inhibition of glycolysis in skeletal muscle of mixed fibre type as a result of increased fatty acid availability. At low rates of glucose flux glycogen synthesis may compensate for decreased glycolysis so that glucose turnover is not decreased. The role of pyruvate dehydrogenase in the “glucose-fatty acid cycle” in muscle may depend on the prevailing plasma insulin concentration and the degree of activation of this enzyme.