![]()
|
|
||||||||
J. Biol. Chem., Vol. 277, Issue 52, 50386-50395, December 27, 2002
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
From the Participation of p38 mitogen-activated protein
kinase (p38) in insulin-induced glucose uptake was suggested using
pyridinylimidazole p38 inhibitors (e.g. SB203580). However,
the role of p38 in insulin action remains controversial. We further
test p38 participation in glucose uptake using a dominant-negative p38
mutant and two novel pharmacological p38 inhibitors related to but
different from SB203580. We present the structures and activities of
the azaazulene pharmacophores A291077 and A304000. p38 kinase activity was inhibited in vitro by A291077 and A304000
(IC50 = 0.6 and 4.7 µM). At higher
concentrations A291077 but not A304000 inhibited JNK2
A Dominant-negative p38 MAPK Mutant and Novel Selective
Inhibitors of p38 MAPK Reduce Insulin-stimulated Glucose Uptake in
3T3-L1 Adipocytes without Affecting GLUT4 Translocation*
§¶,
,
**,
,
,
,
,
,
, and
§§§
Programme in Cell Biology, Hospital for Sick
Children, Toronto, Ontario M5G 1X8, the § Department of
Biochemistry, University of Toronto,
Toronto, Ontario M5S 1A8, Canada,
Diabetes Research,
Pharmaceutical Products Division, Abbott Laboratories, and

Department of Cell Biology, Albert Einstein
College of Medicine, Bronx, New York 10461
(IC50 = 3.5 µM). Pretreatment of 3T3-L1
adipocytes and L6 myotubes expressing GLUT4myc (L6-GLUT4myc myotubes)
with A291077, A304000, SB202190, or SB203580 reduced insulin-stimulated
glucose uptake by 50-60%, whereas chemical analogues inert toward p38 were ineffective. Expression of an inducible, dominant-negative p38
mutant in 3T3-L1 adipocytes reduced insulin-stimulated glucose uptake.
GLUT4 translocation to the cell surface, immunodetected on plasma
membrane lawns of 3T3-L1 adipocytes or on intact L6-GLUT4myc myotubes,
was not altered by chemical or molecular inhibition of p38. We propose
that p38 contributes to enhancing GLUT4 activity, thereby increasing
glucose uptake. In addition, the azaazulene class of inhibitors
described will be useful to decipher cellular actions of p38 and JNK.
*
This work was supported in part by Research Grant MT1202
from the Canadian Institutes for Health Research (to A. K.) and by Grant IR01-DK55758 from the National Institutes of Health (to P. E. S.).The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
This article has been cited by other articles:
![]() |
V. Kaddai, T. Gonzalez, M. Bolla, Y. Le Marchand-Brustel, and M. Cormont The nitric oxide-donating derivative of acetylsalicylic acid, NCX 4016, stimulates glucose transport and glucose transporters translocation in 3T3-L1 adipocytes Am J Physiol Endocrinol Metab, July 1, 2008; 295(1): E162 - E169. [Abstract] [Full Text] [PDF] |
||||
![]() |
B. Emanuelli, D. Eberle, R. Suzuki, and C. R. Kahn Overexpression of the dual-specificity phosphatase MKP-4/DUSP-9 protects against stress-induced insulin resistance PNAS, March 4, 2008; 105(9): 3545 - 3550. [Abstract] [Full Text] [PDF] |
||||
![]() |
B. B. Dokken, V. Saengsirisuwan, J. S. Kim, M. K. Teachey, and E. J. Henriksen Oxidative stress-induced insulin resistance in rat skeletal muscle: role of glycogen synthase kinase-3 Am J Physiol Endocrinol Metab, March 1, 2008; 294(3): E615 - E621. [Abstract] [Full Text] [PDF] |
||||
![]() |
H. F. Kramer and L. J. Goodyear Exercise, MAPK, and NF-{kappa}B signaling in skeletal muscle J Appl Physiol, July 1, 2007; 103(1): 388 - 395. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Choudhary and H.-C. R. Wang Proapoptotic ability of oncogenic H-Ras to facilitate apoptosis induced by histone deacetylase inhibitors in human cancer cells Mol. Cancer Ther., March 1, 2007; 6(3): 1099 - 1111. [Abstract] [Full Text] [PDF] |
||||
![]() |
Y. Xiong, Q. F. Collins, J. An, E. Lupo Jr., H.-Y. Liu, D. Liu, J. Robidoux, Z. Liu, and W. Cao p38 Mitogen-activated Protein Kinase Plays an Inhibitory Role in Hepatic Lipogenesis J. Biol. Chem., February 16, 2007; 282(7): 4975 - 4982. [Abstract] [Full Text] [PDF] |
||||
![]() |
N. Konstantopoulos, S. Marcuccio, S. Kyi, V. Stoichevska, L. A. Castelli, C. W. Ward, and S. L. Macaulay A Purine Analog Kinase Inhibitor, Calcium/Calmodulin-Dependent Protein Kinase II Inhibitor 59, Reveals a Role for Calcium/Calmodulin-Dependent Protein Kinase II in Insulin-Stimulated Glucose Transport Endocrinology, January 1, 2007; 148(1): 374 - 385. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. J. F. P. Luiken, I. Momken, D. D. J. Habets, M. El Hasnaoui, W. A. Coumans, D. P. Y Koonen, J. F. C. Glatz, and A. Bonen Arsenite Modulates Cardiac Substrate Preference by Translocation of GLUT4, But Not CD36, Independent of Mitogen-Activated Protein Kinase Signaling Endocrinology, November 1, 2006; 147(11): 5205 - 5216. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Mari, P. Monzo, V. Kaddai, F. Keslair, T. Gonzalez, Y. Le Marchand-Brustel, and M. Cormont The Rab4 effector Rabip4 plays a role in the endocytotic trafficking of Glut 4 in 3T3-L1 adipocytes J. Cell Sci., April 1, 2006; 119(7): 1297 - 1306. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Turban, V. A. Beardmore, J. M. Carr, K. Sakamoto, E. Hajduch, J. S. C. Arthur, and H. S. Hundal Insulin-Stimulated Glucose Uptake Does Not Require p38 Mitogen-Activated Protein Kinase in Adipose Tissue or Skeletal Muscle Diabetes, November 1, 2005; 54(11): 3161 - 3168. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. Li, E. J. Miller, J. Ninomiya-Tsuji, R. R. Russell III, and L. H. Young AMP-Activated Protein Kinase Activates p38 Mitogen-Activated Protein Kinase by Increasing Recruitment of p38 MAPK to TAB1 in the Ischemic Heart Circ. Res., October 28, 2005; 97(9): 872 - 879. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Yamaguchi, H. Katahira, S. Ozawa, Y. Nakamichi, T. Tanaka, T. Shimoyama, K. Takahashi, K. Yoshimoto, M. O. Imaizumi, S. Nagamatsu, et al. Activators of AMP-activated protein kinase enhance GLUT4 translocation and its glucose transport activity in 3T3-L1 adipocytes Am J Physiol Endocrinol Metab, October 1, 2005; 289(4): E643 - E649. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. N. Antonescu, C. Huang, W. Niu, Z. Liu, P. A. Eyers, K. A. Heidenreich, P. J. Bilan, and A. Klip Reduction of Insulin-Stimulated Glucose Uptake in L6 Myotubes by the Protein Kinase Inhibitor SB203580 Is Independent of p38MAPK Activity Endocrinology, September 1, 2005; 146(9): 3773 - 3781. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Pelletier, E. Joly, M. Prentki, and L. Coderre Adenosine 5'-Monophosphate-Activated Protein Kinase and p38 Mitogen-Activated Protein Kinase Participate in the Stimulation of Glucose Uptake by Dinitrophenol in Adult Cardiomyocytes Endocrinology, May 1, 2005; 146(5): 2285 - 2294. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. Ribe, J. Yang, S. Patel, F. Koumanov, S. W. Cushman, and G. D. Holman Endofacial Competitive Inhibition of Glucose Transporter-4 Intrinsic Activity by the Mitogen-Activated Protein Kinase Inhibitor SB203580 Endocrinology, April 1, 2005; 146(4): 1713 - 1717. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Bazuine, F. Carlotti, M. J. W. E. Rabelink, J. Vellinga, R. C. Hoeben, and J. A. Maassen The p38 Mitogen-Activated Protein Kinase Inhibitor SB203580 Reduces Glucose Turnover by the Glucose Transporter-4 of 3T3-L1 Adipocytes in the Insulin-Stimulated State Endocrinology, April 1, 2005; 146(4): 1818 - 1824. [Abstract] [Full Text] [PDF] |
||||
![]() |
P. C. Geiger, D. C. Wright, D.-H. Han, and J. O. Holloszy Activation of p38 MAP kinase enhances sensitivity of muscle glucose transport to insulin Am J Physiol Endocrinol Metab, April 1, 2005; 288(4): E782 - E788. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. S. Hutchinson and T. Bengtsson {alpha}1A-Adrenoceptors Activate Glucose Uptake in L6 Muscle Cells through a Phospholipase C-, Phosphatidylinositol-3 Kinase-, and Atypical Protein Kinase C-Dependent Pathway Endocrinology, February 1, 2005; 146(2): 901 - 912. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. W. Harmon, D. S. Paul, and Y. M. Patel MEK inhibitors impair insulin-stimulated glucose uptake in 3T3-L1 adipocytes Am J Physiol Endocrinol Metab, October 1, 2004; 287(4): E758 - E766. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. B. Ceddia and G. Sweeney Creatine supplementation increases glucose oxidation and AMPK phosphorylation and reduces lactate production in L6 rat skeletal muscle cells J. Physiol., March 1, 2004; 555(2): 409 - 421. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. C. Ho, O. Alcazar, N. Fujii, M. F. Hirshman, and L. J. Goodyear p38{gamma} MAPK regulation of glucose transporter expression and glucose uptake in L6 myotubes and mouse skeletal muscle Am J Physiol Regulatory Integrative Comp Physiol, February 1, 2004; 286(2): R342 - R349. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Perrini, A. Natalicchio, L. Laviola, G. Belsanti, C. Montrone, A. Cignarelli, V. Minielli, M. Grano, G. De Pergola, R. Giorgino, et al. Dehydroepiandrosterone Stimulates Glucose Uptake in Human and Murine Adipocytes by Inducing GLUT1 and GLUT4 Translocation to the Plasma Membrane Diabetes, January 1, 2004; 53(1): 41 - 52. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Tardif, N. Julien, J.-L. Chiasson, and L. Coderre Stimulation of glucose uptake by chronic vanadate pretreatment in cardiomyocytes requires PI 3-kinase and p38 MAPK activation Am J Physiol Endocrinol Metab, June 1, 2003; 284(6): E1055 - E1064. [Abstract] [Full Text] [PDF] |
||||
![]() |
W. Niu, C. Huang, Z. Nawaz, M. Levy, R. Somwar, D. Li, P. J. Bilan, and A. Klip Maturation of the Regulation of GLUT4 Activity by p38 MAPK during L6 Cell Myogenesis J. Biol. Chem., May 9, 2003; 278(20): 17953 - 17962. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. J. Carlson, S. Koterski, R. J. Sciotti, G. B. Poccard, and C. M. Rondinone Enhanced Basal Activation of Mitogen-Activated Protein Kinases in Adipocytes From Type 2 Diabetes: Potential Role of p38 in the Downregulation of GLUT4 Expression Diabetes, March 1, 2003; 52(3): 634 - 641. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. V. Kandror A Long Search for Glut4 Activation Sci. Signal., February 11, 2003; 2003(169): pe5 - pe5. [Abstract] [Full Text] [PDF] |
||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |