Regulation of glucose uptake by muscle. 8. Effects of fatty acids, ketone bodies and pyruvate, and of alloxan-diabetes and starvation, on the uptake and metabolic fate of glucose in rat heart and diaphragm muscles

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Abstract
The effects of fatty acids and ketone bodies on the uptake and metabolic fate of glucose in rat heart and rat diaphragm were compared with those induced by alloxan-diabetes and starvation. The rate of membrane transport of the pentose L-arabinose was greater in hearts from fed rats than in hearts from rats starved for 18 hr. This difference was attributed to the higher plasma concentration of insulin (which accelerates transport of the pentose) in fed rats. DL-[beta]-Hydroxybutyrate and n-octanoate inhibited L-arabinose transport in hearts from fed rats. In hearts from starved rats transport was not inhibited by these substrates unless insulin was present at a low concentration (0.5 milliunit/ml). At high concentrations of insulin (0.1 unit/ml) these substrates did not inhibit transport. It is suggested that these substrates may impair the sensitivity of the transport system towards stimulation by insulin. Evidence is presented for a similar inhibitory effect of these substrates on glucose transport. In hearts from normal fed rats perfused with medium containing glucose (1 mg/ml) and insulin (0.1 unit/ml) inhibition of glucose uptake and intracellular accumulation of glucose was induced by the addition to the perfusion medium of acetoacetate, DL-[beta]-hydroxybutyrate, butyrate, n-octanoate, pyruvate, and palmitate and oleate (the last 2 as complexes with 2% bovine plasma albumin). It is concluded that these substrates inhibit the phosphorylation of glucose in rat heart. The effects of these substrates on glucose phosphorylation are similar to those previously demonstrated in hearts from diabetic or starved rats. The effects of these substrates on glucose phosphorylation, like those of diabetes or starvation, are abolished by salicylate and by anoxia. When glucose uptake in the perfused rat heart is inhibited by fatty acids, detone bodies or pyruvate, the rate of glycolysis is markedly decreased, whereas the net synthesis of glycogen is either unchanged or increased. Similar effects of butyrate and of palmitate (carried by 0.85% bovine plasma albumin) on the uptake and metabolism of glucose in rat hemidiaphragms have been demonstrated. The output of C14O2 from [1-C14]glucose is greater than that from [6-C14]glucose in perfused rat heart, from which it is inferred that some glucose is oxidized through the pentose phosphate pathway in this tissue. The evidence for the possibility that fatty acids released in vitro from muscle glycerides in muscle from diabetic rats are responsible for impaired rates of glucose transport, glucose phosphorylation, glycolysis, fructose 6-phosphate phosphorylation and oxidation of pyruvate by pyruvate dehydrogenase is summarized and discussed.

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