The functional significance of the plasma free fatty acid (FFA) level as the causal mediator of glucose-fatty acid interactions in striated muscle has been examined in the diaphragm of the intact rat. Acute elevations of the plasma FFA by the fat meal-heparin regimen or the intravenous injection of anti-insulin serum did not result in the intracellular accumulation of free glucose in the rat diaphragm even when glucose transport rates were markedly accelerated by the concomitant administration of a glucose load and insulin, thereby indicating that phosphorylation in this tissue was not significantly depressed by high plasma FFA levels. The tissue FFA level was shown to vary independently of the plasma FFA level (e.g., prolonged starvation, following insulin administration to the seventy-two hour alloxan diabetic rat). The suggestion is made that the tissue fatty acid moiety rather than the plasma FFA level is the major determinant in glucose-fatty acid interactions in striated muscle.

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