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J Biol Chem, Vol. 274, Issue 15, 10071-10078, April 9, 1999
From the The precise mechanisms underlying
insulin-stimulated glucose transport still require investigation. Here
we assessed the effect of SB203580, an inhibitor of the p38 MAP kinase
family, on insulin-stimulated glucose transport in 3T3-L1 adipocytes
and L6 myotubes. We found that SB203580, but not its inactive analogue
(SB202474), prevented insulin-stimulated glucose transport in both cell
types with an IC50 similar to that for inhibition of
p38 MAP kinase (0.6 µM). Basal glucose uptake was not
affected. Moreover, SB203580 added only during the transport assay did
not inhibit basal or insulin-stimulated transport. SB203580 did not
inhibit insulin-stimulated translocation of the glucose transporters
GLUT1 or GLUT4 in 3T3-L1 adipocytes as assessed by immunoblotting of
subcellular fractions or by immunofluorescence of membrane lawns. L6
muscle cells expressing GLUT4 tagged on an extracellular domain with a
Myc epitope (GLUT4myc) were used to assess the functional insertion of
GLUT4 into the plasma membrane. SB203580 did not affect the
insulin-induced gain in GLUT4myc exposure at the cell surface but
largely reduced the stimulation of glucose uptake. SB203580 had no
effect on insulin-dependent insulin receptor substrate-1
phosphorylation, association of the p85 subunit of phosphatidylinositol
3-kinase with insulin receptor substrate-1, nor on phosphatidylinositol
3-kinase, Akt1, Akt2, or Akt3 activities in 3T3-L1 adipocytes. In
conclusion, in the presence of SB203580, insulin caused normal
translocation and cell surface membrane insertion of glucose
transporters without stimulating glucose transport. We propose that
insulin stimulates two independent signals contributing to stimulation
of glucose transport: phosphatidylinositol 3-kinase leads to glucose
transporter translocation and a pathway involving p38 MAP kinase leads
to activation of the recruited glucose transporter at the membrane.
An Inhibitor of p38 Mitogen-activated Protein Kinase Prevents
Insulin-stimulated Glucose Transport but Not Glucose Transporter
Translocation in 3T3-L1 Adipocytes and L6 Myotubes
,§,,§,, and§
Programme in Cell Biology,
Copyright © 1999 by The American Society for Biochemistry and Molecular Biology, Inc.
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C. Y. Christ, D. Hunt, J. Hancock, R. Garcia-Macedo, L. J. Mandarino, and J. L. Ivy Exercise training improves muscle insulin resistance but not insulin receptor signaling in obese Zucker rats J Appl Physiol, February 1, 2002; 92(2): 736 - 744. [Abstract] [Full Text] [PDF]
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 X. Huang, A. Vaag, M. Hansson, and L. Groop Down-Regulation of Insulin Receptor Substrates (IRS)-1 and IRS-2 and Src Homologous and Collagen-Like Protein Shc Gene Expression by Insulin in Skeletal Muscle Is Not Associated with Insulin Resistance or Type 2 Diabetes J. Clin. Endocrinol. Metab., January 1, 2002; 87(1): 255 - 259. [Abstract] [Full Text] [PDF]
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 K. Lange Role of microvillar cell surfaces in the regulation of glucose uptake and organization of energy metabolism Am J Physiol Cell Physiol, January 1, 2002; 282(1): C1 - C26. [Abstract] [Full Text] [PDF]
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 A. R. Shikhman, D. C. Brinson, J. Valbracht, and M. K. Lotz Cytokine Regulation of Facilitated Glucose Transport in Human Articular Chondrocytes J. Immunol., December 15, 2001; 167(12): 7001 - 7008. [Abstract] [Full Text] [PDF]
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R. Somwar, W. Niu, D. Y. Kim, G. Sweeney, V. K. Randhawa, C. Huang, T. Ramlal, and A. Klip Differential Effects of Phosphatidylinositol 3-Kinase Inhibition on Intracellular Signals Regulating GLUT4 Translocation and Glucose Transport J. Biol. Chem., November 30, 2001; 276(49): 46079 - 46087. [Abstract] [Full Text] [PDF]
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 S. Apparsundaram, U. Sung, R. D. Price, and R. D. Blakely Trafficking-Dependent and -Independent Pathways of Neurotransmitter Transporter Regulation Differentially Involving p38 Mitogen-Activated Protein Kinase Revealed in Studies of Insulin Modulation of Norepinephrine Transport in SK-N-SH Cells J. Pharmacol. Exp. Ther., November 1, 2001; 299(2): 666 - 677. [Abstract] [Full Text] [PDF]
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G. Sweeney, J. Keen, R. Somwar, D. Konrad, R. Garg, and A. Klip High Leptin Levels Acutely Inhibit Insulin-Stimulated Glucose Uptake without Affecting Glucose Transporter 4 Translocation in L6 Rat Skeletal Muscle Cells Endocrinology, November 1, 2001; 142(11): 4806 - 4812. [Abstract] [Full Text] [PDF]
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F. Tremblay, C. Lavigne, H. Jacques, and A. Marette Defective Insulin-Induced GLUT4 Translocation in Skeletal Muscle of High Fat-Fed Rats Is Associated With Alterations in Both Akt/Protein Kinase B and Atypical Protein Kinase C ({zeta}/{lambda}) Activities Diabetes, August 1, 2001; 50(8): 1901 - 1910. [Abstract] [Full Text] [PDF]
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N. Spravchikov, G. Sizyakov, M. Gartsbein, D. Accili, T. Tennenbaum, and E. Wertheimer Glucose Effects on Skin Keratinocytes: Implications for Diabetes Skin Complications Diabetes, July 1, 2001; 50(7): 1627 - 1635. [Abstract] [Full Text] [PDF]
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D. Konrad, R. Somwar, G. Sweeney, K. Yaworsky, M. Hayashi, T. Ramlal, and A. Klip The Antihyperglycemic Drug {alpha}-Lipoic Acid Stimulates Glucose Uptake via Both GLUT4 Translocation and GLUT4 Activation: Potential Role of p38 Mitogen-Activated Protein Kinase in GLUT4 Activation Diabetes, June 1, 2001; 50(6): 1464 - 1471. [Abstract] [Full Text]
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J.-Z. Zhang, W. Abbud, R. Prohaska, and F. Ismail-Beigi Overexpression of stomatin depresses GLUT-1 glucose transporter activity Am J Physiol Cell Physiol, May 1, 2001; 280(5): C1277 - C1283. [Abstract] [Full Text] [PDF]
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S. Schneider, W. Chen, J. Hou, C. Steenbergen, and E. Murphy Inhibition of p38 MAPK {alpha}/{beta} reduces ischemic injury and does not block protective effects of preconditioning Am J Physiol Heart Circ Physiol, February 1, 2001; 280(2): H499 - H508. [Abstract] [Full Text] [PDF]
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G. Bandyopadhyay, Y. Kanoh, M. P. Sajan, M. L. Standaert, and R. V. Farese Effects of Adenoviral Gene Transfer of Wild-Type, Constitutively Active, and Kinase-Defective Protein Kinase C-{lambda} on Insulin-Stimulated Glucose Transport in L6 Myotubes Endocrinology, November 1, 2000; 141(11): 4120 - 4127. [Abstract] [Full Text] [PDF]
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J. J. Wilkes and A. Bonen Reduced insulin-stimulated glucose transport in denervated muscle is associated with impaired Akt-alpha activation Am J Physiol Endocrinol Metab, October 1, 2000; 279(4): E912 - E919. [Abstract] [Full Text] [PDF]
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G. Müller, S. Wied, and W. Frick Cross Talk of pp125FAK and pp59Lyn Non-Receptor Tyrosine Kinases to Insulin-Mimetic Signaling in Adipocytes Mol. Cell. Biol., July 1, 2000; 20(13): 4708 - 4723. [Abstract] [Full Text]
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H. Tong, W. Chen, R. E. London, E. Murphy, and C. Steenbergen Preconditioning Enhanced Glucose Uptake Is Mediated by p38 MAP Kinase Not by Phosphatidylinositol 3-Kinase J. Biol. Chem., April 14, 2000; 275(16): 11981 - 11986. [Abstract] [Full Text] [PDF]
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F. V. Lali, A. E. Hunt, S. J. Turner, and B. M. J. Foxwell The Pyridinyl Imidazole Inhibitor SB203580 Blocks Phosphoinositide-dependent Protein Kinase Activity, Protein Kinase B Phosphorylation, and Retinoblastoma Hyperphosphorylation in Interleukin-2-stimulated T Cells Independently of p38 Mitogen-activated Protein Kinase J. Biol. Chem., March 15, 2000; 275(10): 7395 - 7402. [Abstract] [Full Text] [PDF]
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A. S. Blair, E. Hajduch, G. J. Litherland, and H. S. Hundal Regulation of Glucose Transport and Glycogen Synthesis in L6 Muscle Cells during Oxidative Stress. EVIDENCE FOR CROSS-TALK BETWEEN THE INSULIN AND SAPK2/p38 MITOGEN-ACTIVATED PROTEIN KINASE SIGNALING PATHWAYS J. Biol. Chem., December 17, 1999; 274(51): 36293 - 36299. [Abstract] [Full Text] [PDF]
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L. Braiman, A. Alt, T. Kuroki, M. Ohba, A. Bak, T. Tennenbaum, and S. R. Sampson Protein Kinase C{delta} Mediates Insulin-Induced Glucose Transport in Primary Cultures of Rat Skeletal Muscle Mol. Endocrinol., December 1, 1999; 13(12): 2002 - 2012. [Abstract] [Full Text]
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F. Roger, P.-Y. Martin, M. Rousselot, H. Favre, and E. Feraille Cell Shrinkage Triggers the Activation of Mitogen-activated Protein Kinases by Hypertonicity in the Rat Kidney Medullary Thick Ascending Limb of the Henle's Loop. REQUIREMENT OF p38 KINASE FOR THE REGULATORY VOLUME INCREASE RESPONSE J. Biol. Chem., November 26, 1999; 274(48): 34103 - 34110. [Abstract] [Full Text] [PDF]
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S. F. Hausdorff, D. C. Fingar, K. Morioka, L. A. Garza, E. L. Whiteman, S. A. Summers, and M. J. Birnbaum Identification of Wortmannin-sensitive Targets in 3T3-L1 Adipocytes. DISSOCIATION OF INSULIN-STIMULATED GLUCOSE UPTAKE AND GLUT4 TRANSLOCATION J. Biol. Chem., August 27, 1999; 274(35): 24677 - 24684. [Abstract] [Full Text] [PDF]
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R. C. Hresko and M. Mueckler A Novel 68-kDa Adipocyte Protein Phosphorylated on Tyrosine in Response to Insulin and Osmotic Shock J. Biol. Chem., June 9, 2000; 275(24): 18114 - 18120. [Abstract] [Full Text] [PDF]
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Z. Huang, S.-L. Cheng, and E. Slatopolsky Sustained Activation of the Extracellular Signal-regulated Kinase Pathway Is Required for Extracellular Calcium Stimulation of Human Osteoblast Proliferation J. Biol. Chem., June 8, 2001; 276(24): 21351 - 21358. [Abstract] [Full Text] [PDF]
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T. Suzuki, A. Hiroki, T. Watanabe, T. Yamashita, I. Takei, and K. Umezawa Potentiation of Insulin-related Signal Transduction by a Novel Protein-tyrosine Phosphatase Inhibitor, Et-3,4-dephostatin, on Cultured 3T3-L1 Adipocytes J. Biol. Chem., July 13, 2001; 276(29): 27511 - 27518. [Abstract] [Full Text] [PDF]
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M. Fujishiro, Y. Gotoh, H. Katagiri, H. Sakoda, T. Ogihara, M. Anai, Y. Onishi, H. Ono, M. Funaki, K. Inukai, et al. MKK6/3 and p38 MAPK Pathway Activation Is Not Necessary for Insulin-induced Glucose Uptake but Regulates Glucose Transporter Expression J. Biol. Chem., June 1, 2001; 276(23): 19800 - 19806. [Abstract] [Full Text] [PDF]
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X. Xi, J. Han, and J.-Z. Zhang Stimulation of Glucose Transport by AMP-activated Protein Kinase via Activation of p38 Mitogen-activated Protein Kinase J. Biol. Chem., October 26, 2001; 276(44): 41029 - 41034. [Abstract] [Full Text] [PDF]
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H. H. Versteeg, I. Hoedemaeker, S. H. Diks, J. C. Stam, M. Spaargaren, P. M. P. van Bergen en Henegouwen, S. J. H. van Deventer, and M. P. Peppelenbosch Factor VIIa/Tissue Factor-induced Signaling via Activation of Src-like Kinases, Phosphatidylinositol 3-Kinase, and Rac J. Biol. Chem., September 8, 2000; 275(37): 28750 - 28756. [Abstract] [Full Text] [PDF]
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