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Title: Activation of glucose transport in skeletal muscle by phospholipase C and phorbol ester. Evaluation of the regulatory roles of protein kinase C and calcium

It has been hypothesized on the basis of studies on BC3H-1 myocytes that diacylglycerol generation with activation of protein kinase C (PKC) is involved in the stimulation of glucose transport in muscle by insulin. In the present study, we used the rat epitrochlearis muscle to evaluate the possibility that PKC activity mediates the stimulation of glucose transport by insulin in mammalian skeletal muscle. Phospholipase C from Clostridium perfringens (PLC-Cp), which generates diacylglycerol from membrane phospholipids, and 4 beta-phorbol 12 beta-myristate 13 alpha-acetate (PMA) induced increases in glucose transport activity (assessed using 3-O-methylglucose transport) that were approximately 80 and approximately 20% as great, respectively, as that induced by a maximal insulin stimulus. PLC-Cp and PMA both caused a approximately 2-fold increase in membrane-associated PKC activity. In contrast, insulin did not affect PKC activity. These findings argue against a role of diacylglycerol-mediated PKC activation in the stimulation of skeletal muscle glucose transport by insulin. They also show that the BC3H-1 myocyte is not a good model for studying regulation of glucose transport in skeletal muscle. Neither the submaximal nor maximal effects of PLC-Cp and insulin on glucose transport were additive, suggesting that PLC-Cp interferes with insulin action. The maximal effects of PLC-Cpmore » and hypoxia or muscle contractions were also not additive. However, the submaximal effects of hypoxia and PLC-Cp were completely additive. These findings raise the possibility that PLC-Cp stimulates glucose transport by the exercise/hypoxia-activated, not the insulin-activated, pathway in skeletal muscle.« less
Authors:
; ;  [1]
  1. (Washington Univ. School of Medicine, St. Louis, MO (USA))
Publication Date:
OSTI Identifier:
6982954
Resource Type:
Journal Article
Resource Relation:
Journal Name: Journal of Biological Chemistry; (USA); Journal Volume: 264:36
Country of Publication:
United States
Language:
English
Subject:
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.; 59 BASIC BIOLOGICAL SCIENCES; GLUCOSE; MEMBRANE TRANSPORT; INSULIN; BIOCHEMICAL REACTION KINETICS; PHORBOL ESTERS; BIOLOGICAL EFFECTS; PHOSPHOTRANSFERASES; BIOLOGICAL FUNCTIONS; ANOXIA; BIOLOGICAL PATHWAYS; CALCIUM; CONTRACTION; IN VITRO; MUSCLES; RATS; TRACER TECHNIQUES; TRITIUM COMPOUNDS; ALDEHYDES; ALKALINE EARTH METALS; ANIMALS; CARBOHYDRATES; CARCINOGENS; ELEMENTS; ENZYMES; ESTERS; FUNCTIONS; HEXOSES; HORMONES; HYDROGEN COMPOUNDS; ISOTOPE APPLICATIONS; KINETICS; MAMMALS; METALS; MONOSACCHARIDES; ORGANIC COMPOUNDS; PEPTIDE HORMONES; PHOSPHORUS-GROUP TRANSFERASES; REACTION KINETICS; RODENTS; SACCHARIDES; TRANSFERASES; VERTEBRATES 560300* -- Chemicals Metabolism & Toxicology; 550501 -- Metabolism-- Tracer Techniques