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Glucose activates protein kinase C-zeta /lambda through proline-rich tyrosine kinase-2, extracellular signal-regulated kinase, and phospholipase D: A novel mechanism for activating glucose transporter translocation
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2001 (English)In: J Biol Chem, ISSN 0021-9258, Vol. 276, no 38, 35537-45 p.Article in journal (Refereed) Published
Abstract [en]

Insulin controls glucose uptake by translocating GLUT4 and other glucose transporters to the plasma membrane in muscle and adipose tissues by a mechanism that appears to require protein kinase C (PKC)-zeta/lambda operating downstream of phosphatidylinositol 3-kinase. In diabetes mellitus, insulin-stimulated glucose uptake is diminished, but with hyperglycemia, uptake is maintained but by uncertain mechanisms. Presently, we found that glucose acutely activated PKC-zeta/lambda in rat adipocytes and rat skeletal muscle preparations by a mechanism that was independent of phosphatidylinositol 3-kinase but, interestingly, dependent on the apparently sequential activation of the dantrolene-sensitive, nonreceptor proline-rich tyrosine kinase-2; components of the extracellular signal-regulated kinase (ERK) pathway, including, GRB2, SOS, RAS, RAF, MEK1 and ERK1/2; and, most interestingly, phospholipase D, thus yielding increases in phosphatidic acid, a known activator of PKC-zeta/lambda. This activation of PKC-zeta/lambda, moreover, appeared to be required for glucose-induced increases in GLUT4 translocation and glucose transport in adipocytes and muscle cells. Our findings suggest the operation of a novel pathway for activating PKC-zeta/lambda and glucose transport.

Place, publisher, year, edition, pages
2001. Vol. 276, no 38, 35537-45 p.
Keyword [en]
Adipocytes/enzymology/metabolism, Androstadienes/pharmacology, Animals, Dantrolene/pharmacology, Enzyme Inhibitors/pharmacology, Flavonoids/pharmacology, Glucose/*pharmacology, Mitogen-Activated Protein Kinases/*metabolism, Monosaccharide Transport Proteins/metabolism, Muscle Proteins, Muscle; Skeletal/enzymology/metabolism, Phospholipase D/*metabolism, Protein Kinase C/*metabolism, Protein Transport, Protein-Tyrosine Kinase/*metabolism, Rats
URN: urn:nbn:se:uu:diva-73604PubMedID: 11463795OAI: oai:DiVA.org:uu-73604DiVA: diva2:101514
Available from: 2005-06-10 Created: 2005-06-10 Last updated: 2011-01-13

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