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Inhibition of Protein Kinase Cß_II Increases Glucose Uptake in 3T3-L1 Adipocytes through Elevated Expression of Glucose Transporter 1 at the Plasma Membrane

Department of Chemical Endocrinology (R.R.B., M.M.W., P.N.S., A.J.O., C.G.J.S.), Department of Endocrinology (R.R.B., A.R.M.M.H.), and Department of Biochemistry (P.H.G.M.W.), University Medical Centre, 6500 HB Nijmegen, The Netherlands; Department of Molecular Cell Biology (M.B., J.A.M.), Leiden University Medical Center, 2333 AL Leiden, The Netherlands; and Department of Pharmacology (A.S.), German Institute of Human Nutrition, 14588 Potsdam-Rehbrücke, Germany

Address all correspondence and requests for reprints to: R. R. Bosch, Ph.D., Department of Chemical Endocrinology, University Medical Centre Nijmegen, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands. E-mail: R.Bosch{at}ace.umcn.nl.

The mechanism via which diacylglycerol-sensitive protein kinase Cs (PKCs) stimulate glucose transport in insulin-sensitive tissues is poorly defined. Phorbol esters, such as phorbol-12-myristate-13-acetate (PMA), are potent activators of conventional and novel PKCs. Addition of PMA increases the rate of glucose uptake in many different cell systems. We attempted to investigate the mechanism via which PMA stimulates glucose transport in 3T3-L1 adipocytes in more detail. We observed a good correlation between the rate of disappearance of PKCß_II during prolonged PMA treatment and the increase in glucose uptake. Moreover, inhibition of PKCß_II with a specific myristoylated PKCßC2–4 peptide inhibitor significantly increased the rate of glucose transport. Western blot analysis demonstrated that both PMA treatment and incubation with the myristoylated PKCßC2–4 pseudosubstrate resulted in more glucose transporter (GLUT)-1 but not GLUT-4 at the plasma membrane. To our knowledge, we are the first to demonstrate that inactivation of PKC, most likely PKCß_II, elevates glucose uptake in 3T3-L1 adipocytes. The observation that PKCß_II influences the rate of glucose uptake through manipulation of GLUT-1 expression levels at the plasma membrane might reveal a yet unidentified regulatory mechanism involved in glucose homeostasis.

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