|
|
|
|||||||
|
|||||||||
(Received for publication, November 13, 1996, and in revised form, December 31, 1996)
From the Department of Biochemistry and Molecular Biology,
University of Florida, Gainesville, Florida 32610
Insulin resistance is a manifestation of both
diabetes mellitus and obesity. However, the mechanism is still not
clearly identified. Herein, we describe a procedure that allows us to
evaluate the development of insulin resistance in 3T3-L1 adipocytes.
Under these conditions, we show that the concentration of insulin
required for 50% desensitization of glucose transport activity is 100 pM; maximal desensitization could be achieved with 1 nM. This demonstrates for the first time that 3T3-L1
adipocytes develop insulin resistance in response to physiologically
relevant concentrations of insulin. Glucose (or glucosamine), in
addition to insulin, was required to establish desensitization. The
expression of GLUT4 protein decreased by 50% with exposure to 10 nM insulin. The dose-dependent loss of GLUT4
was similar to the dose dependence for insulin-resistant transport
activity. Translocation in the presence of acute insulin was apparent,
but the extent of recruitment directly reflected the decrease in GLUT4
protein. GLUT4 mRNA also declined, but the ED50 was
approximately 5 nM. Together, these data suggest that the
loss of GLUT4 protein likely underlies the cause of desensitization. However, the loss of GLUT4 protein did not correlate with the loss in
GLUT4 mRNA suggesting post-translational control of GLUT4 expression.
Volume 272, Number 12,
Issue of March 21, 1997
pp. 7759-7764
©1997 by The American Society for Biochemistry and Molecular Biology, Inc.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  G. E. Lim, G. J. Huang, N. Flora, D. LeRoith, C. J. Rhodes, and P. L. Brubaker Insulin Regulates Glucagon-Like Peptide-1 Secretion from the Enteroendocrine L Cell Endocrinology, February 1, 2009; 150(2): 580 - 591. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. He, L. Zhu, N. Gupta, Y. Chang, and F. Fang Overexpression of Micro Ribonucleic Acid 29, Highly Up-Regulated in Diabetic Rats, Leads to Insulin Resistance in 3T3-L1 Adipocytes Mol. Endocrinol., November 1, 2007; 21(11): 2785 - 2794. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Bertrand, A. Ginion, C. Beauloye, A. D. Hebert, B. Guigas, L. Hue, and J.-L. Vanoverschelde AMPK activation restores the stimulation of glucose uptake in an in vitro model of insulin-resistant cardiomyocytes via the activation of protein kinase B Am J Physiol Heart Circ Physiol, July 1, 2006; 291(1): H239 - H250. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Yang and G. D. Holman Long-Term Metformin Treatment Stimulates Cardiomyocyte Glucose Transport through an AMP-Activated Protein Kinase-Dependent Reduction in GLUT4 Endocytosis Endocrinology, June 1, 2006; 147(6): 2728 - 2736. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. G. Buse Hexosamines, insulin resistance, and the complications of diabetes: current status Am J Physiol Endocrinol Metab, January 1, 2006; 290(1): E1 - E8. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. C. Love and J. A. Hanover The Hexosamine Signaling Pathway: Deciphering the "O-GlcNAc Code" Sci. Signal., November 29, 2005; 2005(312): re13 - re13. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. H. Mulder, C. J. Tack, A. J. Olthaar, P. Smits, F. C. G. J. Sweep, and R. R. Bosch Adrenergic receptor stimulation attenuates insulin-stimulated glucose uptake in 3T3-L1 adipocytes by inhibiting GLUT4 translocation Am J Physiol Endocrinol Metab, October 1, 2005; 289(4): E627 - E633. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. A. McClain, M. Hazel, G. Parker, and R. C. Cooksey Adipocytes with increased hexosamine flux exhibit insulin resistance, increased glucose uptake, and increased synthesis and storage of lipid Am J Physiol Endocrinol Metab, May 1, 2005; 288(5): E973 - E979. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Cordain, S B. Eaton, A. Sebastian, N. Mann, S. Lindeberg, B. A Watkins, J. H O'Keefe, and J. Brand-Miller Origins and evolution of the Western diet: health implications for the 21st century Am. J. Clinical Nutrition, February 1, 2005; 81(2): 341 - 354. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C.-K. Hyun, I.-Y. Kim, and S. C. Frost Soluble Fibroin Enhances Insulin Sensitivity and Glucose Metabolism in 3T3-L1 Adipocytes J. Nutr., December 1, 2004; 134(12): 3257 - 3263. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Kumar, Y.-P. Xiao, P. J. Laipis, B. S. Fletcher, and S. C. Frost Glucose deprivation enhances targeting of GLUT1 to lipid rafts in 3T3-L1 adipocytes Am J Physiol Endocrinol Metab, April 1, 2004; 286(4): E568 - E576. [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]
|
|
|
|
 |
|
 D. A. McClain, W. A. Lubas, R. C. Cooksey, M. Hazel, G. J. Parker, D. C. Love, and J. A. Hanover Altered glycan-dependent signaling induces insulin resistance and hyperleptinemia PNAS, August 6, 2002; 99(16): 10695 - 10699. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Huang, R. Somwar, N. Patel, W. Niu, D. Torok, and A. Klip Sustained Exposure of L6 Myotubes to High Glucose and Insulin Decreases Insulin-Stimulated GLUT4 Translocation but Upregulates GLUT4 Activity Diabetes, July 1, 2002; 51(7): 2090 - 2098. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. O. Broschat, C. Gorka, J. D. Page, C. L. Martin-Berger, M. S. Davies, H.-c. Huang, E. A. Gulve, W. J. Salsgiver, and T. P. Kasten Kinetic Characterization of Human Glutamine-fructose-6-phosphate Amidotransferase I. POTENT FEEDBACK INHIBITION BY GLUCOSAMINE 6-PHOSPHATE J. Biol. Chem., April 19, 2002; 277(17): 14764 - 14770. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Vosseller, L. Wells, M. D. Lane, and G. W. Hart Elevated nucleocytoplasmic glycosylation by O-GlcNAc results in insulin resistance associated with defects in Akt activation in 3T3-L1 adipocytes PNAS, April 16, 2002; 99(8): 5313 - 5318. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Tardif, N. Julien, A. Pelletier, G. Thibault, A. K. Srivastava, J.-L. Chiasson, and L. Coderre Chronic exposure to beta -hydroxybutyrate impairs insulin action in primary cultures of adult cardiomyocytes Am J Physiol Endocrinol Metab, December 1, 2001; 281(6): E1205 - E1212. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. M. Pederson, D. L. Kramer, and C. M. Rondinone Serine/Threonine Phosphorylation of IRS-1 Triggers Its Degradation: Possible Regulation by Tyrosine Phosphorylation Diabetes, January 1, 2001; 50(1): 24 - 31. [Abstract] [Full Text]
|
|
|
|
|
|
K.-i. Ishibashi, T. Imamura, P. M. Sharma, S. Ugi, and J. M. Olefsky The Acute and Chronic Stimulatory Effects of Endothelin-1 on Glucose Transport Are Mediated by Distinct Pathways in 3T3-L1 Adipocytes Endocrinology, December 1, 2000; 141(12): 4623 - 4628. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Heart, W. S. Choi, and C. K. Sung Glucosamine-induced insulin resistance in 3T3-L1 adipocytes Am J Physiol Endocrinol Metab, January 1, 2000; 278(1): E103 - E112. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. B. Hwang and S. C. Frost Effect of Alternative Glycosylation on Insulin Receptor Processing J. Biol. Chem., August 6, 1999; 274(32): 22813 - 22820. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Stumpel, T. Kucera, and K. Jungermann Impaired stimulation of intestinal glucose absorption via hepatoenteral nerves in streptozotocin-diabetic rats Am J Physiol Gastrointest Liver Physiol, August 1, 1999; 277(2): G285 - G291. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Wang, W. Lee-Kwon, J. L. Martindale, L. Adams, P. Heller, J. M. Egan, and M. Bernier Modulation of CCAAT/Enhancer-Binding Protein-{alpha} Gene Expression by Metabolic Signals in Rodent Adipocytes Endocrinology, July 1, 1999; 140(7): 2938 - 2947. [Abstract] [Full Text]
|
|
|
|
|
|
L.-y. Qiao, J. L. Goldberg, J. C. Russell, and X. J. Sun Identification of Enhanced Serine Kinase Activity in Insulin Resistance J. Biol. Chem., April 9, 1999; 274(15): 10625 - 10632. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. C. Hresko, H. Heimberg, M. M.-Y. Chi, and M. Mueckler Glucosamine-induced Insulin Resistance in 3T3-L1 Adipocytes Is Caused by Depletion of Intracellular ATP J. Biol. Chem., August 7, 1998; 273(32): 20658 - 20668. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Q. Chang, K. Su, J. R. Baker, X. Yang, A. J. Paterson, and J. E. Kudlow Phosphorylation of Human Glutamine:Fructose-6-phosphate Amidotransferase by cAMP-dependent Protein Kinase at Serine 205 Blocks the Enzyme Activity J. Biol. Chem., July 14, 2000; 275(29): 21981 - 21987. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. C. Jensen, S. M. Crosson, P. M. Kartha, and M. J. Brady Specific Desensitization of Glycogen Synthase Activation by Insulin in 3T3-L1 Adipocytes. CONNECTION BETWEEN ENZYMATIC ACTIVATION AND SUBCELLULAR LOCALIZATION J. Biol. Chem., December 15, 2000; 275(51): 40148 - 40154. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Dowell and D. W. Cooke Olf-1/Early B Cell Factor Is a Regulator of glut4 Gene Expression in 3T3-L1 Adipocytes J. Biol. Chem., January 11, 2002; 277(3): 1712 - 1718. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. A. Nelson, K. A. Robinson, and M. G. Buse Defective Akt activation is associated with glucose- but not glucosamine-induced insulin resistance Am J Physiol Endocrinol Metab, March 1, 2002; 282(3): E497 - E506. [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 |