Insulin mediator causes dephosphorylation of the alpha subunit of pyruvate dehydrogenase by stimulating phosphatase activity.
Insulin treatment of rats results in an increased amount or activity of insulin mediators in liver and skeletal muscle. These mediators stimulated pyruvate dehydrogenase and inhibited adenylate cyclase. The insulin-generated mediators caused dephosphorylation of the alpha subunit of pyruvate dehydrogenase in mitochondria prelabeled with [gamma-32P]ATP. An assay was developed which quantitatively measured mediator activity by determining the rate of alpha-subunit dephosphorylation. The dephosphorylation was directly proportional to the amount of mediator added and was directly related to activation of pyruvate dehydrogenase. The decrease of alpha-subunit phosphorylation resulted from stimulation of pyruvate dehydrogenase phosphatase, since it occurred in the absence of ATP and was inhibited by NaF. These data further delineate the mechanism of insulin mediator activation of pyruvate dehydrogenase.
Macaulay
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Jarett
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D000262:Adenylyl Cyclases / Q000378:metabolism; D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D004789:Enzyme Activation; D007295:Inositol Phosphates; D008099:Liver / Q000378:metabolism; D008297:Male; D008928:Mitochondria / Q000378:metabolism; D009132:Muscles / Q000378:metabolism; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D011134:Polysaccharides; D011769:Pyruvate Dehydrogenase (Lipoamide)-Phosphatase / Q000378:metabolism*; D011768:Pyruvate Dehydrogenase Complex / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011972:Receptor, Insulin / Q000502:physiology*
D007295:Inositol Phosphates; D011134:Polysaccharides; D011768:Pyruvate Dehydrogenase Complex; C028039:inositol phosphate glycan; D011972:Receptor, Insulin; D010749:Phosphoprotein Phosphatases; D011769:Pyruvate Dehydrogenase (Lipoamide)-Phosphatase; D000262:Adenylyl Cyclases