Abstract
Pyruvate dehydrogenase activity of rat adipose tissue is considerably increased upon incubation with insulin due to conversion of the inactive phospho form (PDH b) to the active dephospho form (PDH a) of the enzyme. This effect depends on the presence of a metabolizable sugar such as glucose, fructose, mannose, or deoxyglucose. With pyruvate as a substrate PDH activation occurs already in the absence of insulin. Whereas nicotinate and other antilipolytic agents produced similar effects as insulin prostaglandin E1 remained ineffective under standard conditions. When adipose tissue from fasted-refed rats was taken, which is rich in glycogen, prostaglandin E1, and also insulin, led to PDH activation without the need for exogenous glucose.
Further studies carried out on isolated fat cell mitochondria pointed to the possibility that changes in mitochondrial adenine nucleotides (AN) may be involved in PDH interconversion by insulin. Increasing the ADP/ATP ratio by addition of hexokinase-glucose to mitochondrial suspensions resulted in an increase of PDH a/PDH b,whereas a decrease of ADP/ATP due to AN translocase inhibition either by atractylate or by palmityl-CoA had the opposite effect. In view of the observation that insulin lowers long chain acyl-CoA levels in adipose tissue (Denton and Halperin, 1968) its activating effect on the PDH-system may result from an increase of the mitochondrial ADP/ATP ratio due to deinhibition of AN translocase activity. The role of substrate in the mechanism of insulin action may thus in part be explained by giving rise to α-glycerophosphate which acts in lowering of long chain acyl-CoA levels due to increased re-esterification.
Supported by the Deutsche Forschungsgemeinschaft, Bad Godesberg.
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Wieland, O.H., Weiss, L., Löffler, G., Brunner, I., Bard, S. (1974). On the Mechanism of Insulin Action on Pyruvate Dehydrogenase Interconversion in Adipose Tissue. In: Metabolic Interconversion of Enzymes 1973. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-80817-3_12
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