Knockout of the predominant conventional PKC isoform, PKCalpha, in mouse skeletal muscle does not affect contraction-stimulated glucose uptake

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Conventional (c) protein kinase C (PKC) activity has been shown to increase with skeletal muscle contraction, and numerous studies using primarily pharmacological inhibitors have implicated cPKCs in contraction-stimulated glucose uptake. Here, to confirm that cPKC activity is required for contraction-stimulated glucose uptake in mouse muscles, contraction-stimulated glucose uptake ex vivo was first evaluated in the presence of three commonly used cPKC inhibitors (calphostin C, Gö-6976, and Gö-6983) in incubated mouse soleus and extensor digitorum longus (EDL) muscles. All potently inhibited contraction-stimulated glucose uptake by 50-100%, whereas both Gö compounds, but not calphostin C, inhibited insulin-stimulated glucose uptake modestly. AMP-activated protein kinase (AMPK) and eukaryotic elongation factor 2 phosphorylation was unaffected by the blockers. PKCalpha was estimated to account for approximately 97% of total cPKC protein expression in skeletal muscle. However, in muscles from PKCalpha knockout (KO) mice, neither contraction- nor phorbol ester-stimulated glucose uptake ex vivo differed compared with the wild type. Furthermore, the effects of calphostin C and Gö-6983 on contraction-induced glucose uptake were similar in muscles lacking PKCalpha and in the wild type. It can be concluded that PKCalpha, representing approximately 97% of cPKC in skeletal muscle, is not required for contraction-stimulated glucose uptake. Thus the effect of the PKC blockers on glucose uptake is either nonspecific working on other parts of contraction-induced signaling or the remaining cPKC isoforms are sufficient for stimulating glucose uptake during contractions.
Original languageEnglish
JournalAmerican Journal of Physiology: Endocrinology and Metabolism
Issue number2
Pages (from-to)E340-E348
Number of pages9
Publication statusPublished - 2009

Bibliographical note

Keywords: Animals; Biological Transport; Carbazoles; Enzyme Inhibitors; Glucose; Isoenzymes; Male; Mice; Mice, Knockout; Muscle Contraction; Muscle, Skeletal; Naphthalenes; Phosphorylation; Protein Kinase C-alpha

ID: 13916589