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Developmentally spliced PKCbetaII provides a possible link between mTORC2 and Akt kinase to regulate 3T3-L1 adipocyte insulin-stimulated glucose transport.

ABSTRACT: Functional adipocyte glucose disposal is a key component of global glucose homeostasis. PKCbetaII is involved in rat skeletal muscle cell ISGT. Western blot analysis and real-time PCR revealed 3T3-L1 cells developmentally regulated PKCbeta splicing such that PKCbetaI was downregulated and PKCbetaII was upregulated during the course of differentiation. An initial glucose uptake screen using PKC inhibitor LY379196 pointed to a PKC isozyme other than PKCzeta mediating 3T3-L1 adipocyte ISGT. Subsequent use of PKCbetaII inhibitor CGP53353 pointed to a role for PKCbetaII in ISGT. Western blot analysis showed that CGP53353 specifically inhibited phosphorylation of PKCbetaII Serine 660. Subcellular fractionation and immunofluorescence demonstrated that PKCbetaII regulates GLUT4 translocation. Further Western blot, immunofluorescence and co-immunoprecipitation analysis reveal that PKCbetaII inhibition does not affect mTORC2 activity yet abrogates phosphorylation of Akt Serine 473. PKCbetaII regulates GLUT4 translocation by regulating Akt phosphorylation and thus activity.

SUBMITTER: Kleiman E

PROVIDER: S-EPMC3033743 | biostudies-literature | 2009 Oct

REPOSITORIES: biostudies-literature

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Developmentally spliced PKCbetaII provides a possible link between mTORC2 and Akt kinase to regulate 3T3-L1 adipocyte insulin-stimulated glucose transport.

Kleiman E E Carter G G Ghansah T T Patel N A NA Cooper D R DR

Biochemical and biophysical research communications 20090815 3

Functional adipocyte glucose disposal is a key component of global glucose homeostasis. PKCbetaII is involved in rat skeletal muscle cell ISGT. Western blot analysis and real-time PCR revealed 3T3-L1 cells developmentally regulated PKCbeta splicing such that PKCbetaI was downregulated and PKCbetaII was upregulated during the course of differentiation. An initial glucose uptake screen using PKC inhibitor LY379196 pointed to a PKC isozyme other than PKCzeta mediating 3T3-L1 adipocyte ISGT. Subsequ ...[more]

PMID: 19686698

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Dataset Information

Developmentally spliced PKCbetaII provides a possible link between mTORC2 and Akt kinase to regulate 3T3-L1 adipocyte insulin-stimulated glucose transport.

Publications

Developmentally spliced PKCbetaII provides a possible link between mTORC2 and Akt kinase to regulate 3T3-L1 adipocyte insulin-stimulated glucose transport.

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