Activation of pyruvate dehydrogenase in adipose tissue by insulin. Evidence for an effect of insulin on pyruvate dehydrogenase phosphate phosphatase

Mukherjee, Chhabirani; Jungas, Robert L.

doi:10.1042/bj1480229

Cited by 58 publications

(16 citation statements)

References 22 publications

(27 reference statements)

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“…(Coore & Field, 1974). Similar slow rates of inactivation of pyruvate dehydrogenase by ATP have been observed in adipose-tissue homogenates (Mukherjee & Jungas, 1975 (Cooper et al, 1974). In the experiments of Fig.…”

Section: Resultssupporting

confidence: 64%

The mode of regulation of pyruvate dehydrogenase of lactating rat mammary gland. Effects of starvation and insulin

Baxter

Coore

1978

Biochemical Journal

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1. The ‘initial activity’ of the pyruvate dehydrogenase enzyme complex in whole tissue or mitochondrial extracts of lactating rat mammary glands was greatly decreased by 24 or 48h starvation of the rats. Injection of insulin and glucose into starved rats 60min before removal of the glands abolished this difference in ‘initial activities’. 2. The ‘total activity’ of the enzyme complex in such extracts was revealed by incubation in the presence of free Mg2+ and Ca2+ ions (more than 10 and 0.1mm respectively) and a crude preparation of pig heart pyruvate dehydrogenase phosphatase. Starvation did not alter this ‘total activity’. It is assumed that the decline in ‘initial activity’ of the enzyme complex derived from the glands of starved animals was due to increased phosphorylation of its α-subunit by intrinsic pyruvate dehydrogenase kinase. 3. Starvation led to an increase in intrinsic pyruvate dehydrogenase kinase activity in both whole tissue and mitochondrial extracts. Injection of insulin into starved animals 30min before removal of the lactating mammary glands abolished the increase in pyruvate dehydrogenase kinase activity in whole-tissue extracts. 4. Pyruvate (1mm) prevented ATP-induced inactivation of the enzyme complex in mitochondrial extracts from glands of fed animals. In similar extracts from starved animals pyruvate was ineffective. 5. Starvation led to a decline in activity of pyruvate dehydrogenase phosphatase in mitochondrial extracts, but not in whole-tissue extracts. 6. These changes in activity of the intrinsic kinase and phosphatase of the pyruvate dehydrogenase complex of lactating rat mammary gland are not explicable by current theories of regulation of the complex.

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Section: Resultssupporting

confidence: 64%

The mode of regulation of pyruvate dehydrogenase of lactating rat mammary gland. Effects of starvation and insulin

Baxter

Coore

1978

Biochemical Journal

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“…A major effect of insulin is to increase the activity of the pyruvate dehydrogenase multienzyme complex ( 21,22 ), thus increasing the provision of acetyl-CoA for use in the Krebs cycle.…”

Section: Feeding Ketone Body Esters Tomentioning

confidence: 99%

Ketone ester effects on metabolism and transcription

Veech

2014

Journal of Lipid Research

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“…The PDH complex is inactivated by phosphorylation accomplished by a PDH kinase (4,6,7). PDH phosphatases dephosphorylate the PDH complex and reactivate the complex (8,9). The relative activities of PDH kinase and phosphatase determine the proportion of PDH in the active dephosphorylated form.…”

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confidence: 99%

Activation and Mitochondrial Translocation of Protein Kinase Cδ Are Necessary for Insulin Stimulation of Pyruvate Dehydrogenase Complex Activity in Muscle and Liver Cells

Caruso

Maitan

Bifulco

et al. 2001

Journal of Biological Chemistry

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In L6 skeletal muscle cells and immortalized hepatocytes, insulin induced a 2-fold increase in the activity of the pyruvate dehydrogenase (PDH) complex. This effect was almost completely blocked by the protein kinase C (PKC) ␦ inhibitor Rottlerin and by PKC␦ antisense oligonucleotides. At variance, overexpression of wild-type PKC␦ or of an active PKC␦ mutant induced PDH complex activity in both L6 and liver cells. Insulin stimulation of the activity of the PDH complex was accompanied by a 2.5-fold increase in PDH phosphatases 1 and 2 (PDP1/2) activity with no change in the activity of PDH kinase. PKC␦ antisense blocked insulin activation of PDP1/2, the same as with PDH. In insulin-exposed cells, PDP1/2 activation was paralleled by activation and mitochondrial translocation of PKC␦, as revealed by cell subfractionation and confocal microscopy studies. The mitochondrial translocation of PKC␦, like its activation, was prevented by Rottlerin. In extracts from insulinstimulated cells, PKC␦ co-precipitated with PDP1/2. PKC␦ also bound to PDP1/2 in overlay blots, suggesting that direct PKC␦-PDP interaction may occur in vivo as well. In intact cells, insulin exposure determined PDP1/2 phosphorylation, which was specifically prevented by PKC␦ antisense. PKC␦ also phosphorylated PDP in vitro, followed by PDP1/2 activation. Thus, in muscle and liver cells, insulin causes activation and mitochondrial translocation of PKC␦, accompanied by PDP phosphorylation and activation. These events are necessary for insulin activation of the PDH complex in these cells.

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Activation of pyruvate dehydrogenase in adipose tissue by insulin. Evidence for an effect of insulin on pyruvate dehydrogenase phosphate phosphatase

Cited by 58 publications

References 22 publications

The mode of regulation of pyruvate dehydrogenase of lactating rat mammary gland. Effects of starvation and insulin

The mode of regulation of pyruvate dehydrogenase of lactating rat mammary gland. Effects of starvation and insulin

Ketone ester effects on metabolism and transcription

Activation and Mitochondrial Translocation of Protein Kinase Cδ Are Necessary for Insulin Stimulation of Pyruvate Dehydrogenase Complex Activity in Muscle and Liver Cells

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