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Differential Effect of PKC Isoform on Insulin‐ and Phorbol Ester‐Stimulated Glucose Uptake Mechanism in Rat Adipocytes
Author(s) -
Ishizuka Tatsuo,
Miura Atsushi,
Kajita Kazuo,
Ishizawa Masayoshi,
Kimura Mika,
Huang Yannan,
Kawai Yasunori,
Morita Hiroyuki,
Uno Yoshihiro,
Yasuda Keigo
Publication year - 2001
Publication title -
iubmb life
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.132
H-Index - 113
eISSN - 1521-6551
pISSN - 1521-6543
DOI - 10.1080/152165401317190806
Subject(s) - protein kinase c , wortmannin , glucose uptake , insulin , medicine , endocrinology , phosphatidylinositol , phorbol , snf3 , glucose transporter , kinase , chemistry , biology , biochemistry
Insulin stimulates glucose uptake in association with phosphatidylinositol (PI) 3‐kinase activation mechanisms in rat adipocytes. Insulin stimulated glucose uptake to 6.5‐fold, and 12‐ o ‐tetradecanoyl phorbol 13‐acetate (TPA) also stimulated glucose uptake to 4.5‐fold in rat adipocytes. We examined these differences in glucose uptake, PKC ∂activation, and PI 3‐kinase activation after stimulation with insulin and TPA. TPA stimulated PI 3‐kinase activity and increased the p85 subunit of PI 3‐kinase immunoreactivity in anti‐phosphotyrosine antibody‐immunoprecipitated protein. Insulin and TPA provoked increases in membrane PKC ∂immunoreactivity.The PI 3‐kinase inhibitor,wortmannin, suppressed insulininduced increases in glucose uptake, PI 3‐kinase activity, and PKC ∂activation. Wortmannin also suppressed TPA‐induced PI 3‐kinase activity and PKC ∂activation but suppressed TPA‐induced glucose uptake to only a small extent. The PKC inhibitor, Go6976, which only inhibits conventional PKC αand _, suppressed TPA‐induced glucose uptake, but suppressed insulin‐induced glucose uptake to only a small extent. On the other hand, the PKC inhibitor, RO32‐0432, which inhibits conventional, novel, and atypical PKCs, markedly suppressed both insulin‐ and TPA‐induced glucose uptake. These results suggest that insulininduced glucose uptake is mainly mediated by PI 3‐kinase‐PKC ∂signaling, whereas phorbol ester‐induced glucose uptake is mainly mediated by conventional PKC despite PI 3‐kinase and PKC ∂activations.