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PKCβ knockout blocks insulin stimulated IRS1ser307 phosphorylation
Author(s) -
Zwetsloot Jennifer,
Tapscott Edward,
Buttrick Peter,
Leitges Michael,
Dohm G. Lynis
Publication year - 2006
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.20.4.a299-c
Subject(s) - irs1 , medicine , protein kinase c , insulin , insulin receptor , endocrinology , insulin resistance , phosphorylation , tyrosine phosphorylation , insulin receptor substrate , signal transduction , irs2 , chemistry , biology , microbiology and biotechnology
Insulin resistance is marked by a reduction of insulin stimulated glucose uptake and insulin signal transduction. In incubated muscle from obese patients we observed decreases in insulin activation of insulin receptor substrate 1 (IRS1) tyrosine phosphorylation. We also found increased protein kinase C beta (PKCβ) activity and IRS1ser312 (mouse ser307) phosphorylation, both of which are suspected as mechanisms of decreased insulin signal transduction in insulin resistance. Recently, we showed that pre‐incubating obese skeletal muscle with AICAR reduced insulin stimulation of both PKCβ and IRS1ser312 phosphorylation. The purpose of this study was to further investigate this relationship by examining the effect of insulin on IRS1 serine phosphorylation and insulin signaling activity in PKCβ knockout mice (PKCβKO). Gastrocnemius muscles from PKCβKO and wild type (WT) littermates treated with and without insulin were analyzed. Insulin increased phosphorylation of IRS1ser307 by 58% over basal in WT. This increase was abolished in the PKCβKO. Inversely, insulin stimulated IRS1 tyrosine phosphorylation was significantly higher in PKCβKO compared to WT (305% over basal vs. 111% respectively). Insulin stimulated IRS1 association of PI3K was also increased in PKCβKO vs. WT (172% vs. 86% respectively). These data indicate that insulin stimulated IRS1ser307 phosphorylation is indeed mediated by PKCβ. The project was supported by a grant from the NIH (R01 DK046121).