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Differential effect of PKC isoform on insulin- and phorbol ester-stimulated glucose uptake mechanism in rat adipocytes. 2001

T Ishizuka, and A Miura, and K Kajita, and M Ishizawa, and M Kimura, and Y Huang, and Y Kawai, and H Morita, and Y Uno, and K Yasuda
Department of General Medicine, Gifu University School of Medicine, Japan. tishizuk-gif@umin.ac.jp

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.

UI MeSH Term Description Entries
D007211 Indoles Benzopyrroles with the nitrogen at the number one carbon adjacent to the benzyl portion, in contrast to ISOINDOLES which have the nitrogen away from the six-membered ring.
D007328 Insulin A 51-amino acid pancreatic hormone that plays a major role in the regulation of glucose metabolism, directly by suppressing endogenous glucose production (GLYCOGENOLYSIS; GLUCONEOGENESIS) and indirectly by suppressing GLUCAGON secretion and LIPOLYSIS. Native insulin is a globular protein comprised of a zinc-coordinated hexamer. Each insulin monomer containing two chains, A (21 residues) and B (30 residues), linked by two disulfide bonds. Insulin is used as a drug to control insulin-dependent diabetes mellitus (DIABETES MELLITUS, TYPE 1). Iletin,Insulin A Chain,Insulin B Chain,Insulin, Regular,Novolin,Sodium Insulin,Soluble Insulin,Chain, Insulin B,Insulin, Sodium,Insulin, Soluble,Regular Insulin
D008297 Male Males
D011493 Protein Kinase C An serine-threonine protein kinase that requires the presence of physiological concentrations of CALCIUM and membrane PHOSPHOLIPIDS. The additional presence of DIACYLGLYCEROLS markedly increases its sensitivity to both calcium and phospholipids. The sensitivity of the enzyme can also be increased by PHORBOL ESTERS and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters. Calcium Phospholipid-Dependent Protein Kinase,Calcium-Activated Phospholipid-Dependent Kinase,PKC Serine-Threonine Kinase,Phospholipid-Sensitive Calcium-Dependent Protein Kinase,Protein Kinase M,Calcium Activated Phospholipid Dependent Kinase,Calcium Phospholipid Dependent Protein Kinase,PKC Serine Threonine Kinase,Phospholipid Sensitive Calcium Dependent Protein Kinase,Phospholipid-Dependent Kinase, Calcium-Activated,Serine-Threonine Kinase, PKC
D011758 Pyrroles Azoles of one NITROGEN and two double bonds that have aromatic chemical properties. Pyrrole
D003847 Deoxyglucose 2-Deoxy-D-arabino-hexose. An antimetabolite of glucose with antiviral activity. 2-Deoxy-D-glucose,2-Deoxyglucose,2-Desoxy-D-glucose,2 Deoxy D glucose,2 Deoxyglucose,2 Desoxy D glucose
D004789 Enzyme Activation Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme. Activation, Enzyme,Activations, Enzyme,Enzyme Activations
D004791 Enzyme Inhibitors Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction. Enzyme Inhibitor,Inhibitor, Enzyme,Inhibitors, Enzyme
D005947 Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Dextrose,Anhydrous Dextrose,D-Glucose,Glucose Monohydrate,Glucose, (DL)-Isomer,Glucose, (alpha-D)-Isomer,Glucose, (beta-D)-Isomer,D Glucose,Dextrose, Anhydrous,Monohydrate, Glucose
D000077191 Wortmannin An androstadiene metabolite produced by the fungi PENICILLIUM funiculosum that inhibits PHOSPHATIDYLINOSITOL-3-KINASES and alloantigen-specific activation of T-LYMPHOCYTES in human tumor cell lines. It is widely used in CELL BIOLOGY research and has broad therapeutic potential. MS 54,MS-54,MS54

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