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Phosphorylation of rat skeletal muscle pyruvate dehydrogenase phosphatase in response to insulin stimulation
Author(s) -
Choptiany Jonathan,
MacPherson Rebecca,
LeBlanc Paul,
Peters Sandra
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1208.1
Subject(s) - pyruvate dehydrogenase complex , insulin , medicine , stimulation , pdk4 , pyruvate dehydrogenase kinase , endocrinology , phosphorylation , protein kinase c , phosphatase , pyruvate decarboxylation , mitochondrion , skeletal muscle , biology , chemistry , biochemistry , enzyme
Pyruvate dehydrogenase phosphatase (PDP) regulates carbohydrate oxidation through the mitochondrial pyruvate dehydrogenase (PDH) complex. PDP dephosphorylates and activates PDH, enabling increased carbohydrate flux towards oxidative energy production. In cell culture, both PDP1 and 2 appear to undergo covalent activation in direct response to insulin–stimulation by PKCδ. Our objective was to examine the effect of insulin on PDP phosphorylation and PDH activation. Intact rat extensor digitorum longus muscles were incubated (oxygenated at 25°C, fixed to 1g of resting tension) tendon–to–tendon for 30min in basal or insulin–stimulated (10mU/mL) media. PDH activity increased 58% following insulin stimulation, (p=0.057, n=11). Serine phosphorylation of PDP1 (p=0.037) and PDP2 (p=0.027) increased by 44% and 54% respectively following stimulation (n=4), and PKCδ protein content was enriched in the mitochondrial fraction by 45% in response to insulin stimulation (p=0.0009, n=8). These data suggest that the insulin–stimulated increase in PDH activity in whole tissue is mediated through mitochondrial migration of PKCδ and subsequent PDP phosphorylation. Research supported by NSERC, Canada.