Differential effect of PKC isoform on insulin- and phorbol ester-stimulated glucose uptake mechanism in rat adipocytes.
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, PKCzeta 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 PKCzeta immunoreactivity. The PI 3-kinase inhibitor, wortmannin, suppressed insulin-induced increases in glucose uptake, PI 3-kinase activity, and PKCzeta activation. Wortmannin also suppressed TPA-induced PI 3-kinase activity and PKCzeta activation but suppressed TPA-induced glucose uptake to only a small extent. The PKC inhibitor, Go6976, which only inhibits conventional PKCalpha and _, 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 insulin-induced glucose uptake is mainly mediated by PI 3-kinase-PKCzeta signaling, whereas phorbol ester-induced glucose uptake is mainly mediated by conventional PKC despite PI 3-kinase and PKCzeta activations.
Ishizuka
T
T
Department of General Medicine, Gifu University School of Medicine, Japan. tishizuk-gif@umin.ac.jp
Miura
A
A
Kajita
K
K
Ishizawa
M
M
Kimura
M
M
Huang
Y
Y
Kawai
Y
Y
Morita
H
H
Uno
Y
Y
Yasuda
K
K
D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism*; D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D003847:Deoxyglucose / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism*; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology*; D008297:Male; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011493:Protein Kinase C / Q000378:metabolism*; D011758:Pyrroles / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D000077191:Wortmannin; D000099221:Protein Kinase C zeta
D000730:Androstadienes; D003847:Deoxyglucose; D004791:Enzyme Inhibitors; D005947:Glucose; D007211:Indoles; D007328:Insulin; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011493:Protein Kinase C; D011758:Pyrroles; D013755:Tetradecanoylphorbol Acetate; D000077191:Wortmannin; D000099221:Protein Kinase C zeta; C085989:Ro 32-0432