| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
agonists) but not PPAR
agonists increase IRS-2 gene expression in 3T3-L1 and human adipocytes1
The Lundberg Laboratory for Diabetes Research, Department of Internal Medicine, Goteborg University, Sahlgrenska University Hospital, S-413 45 Goteborg, Sweden
2Correspondence: The Lundberg Laboratory for Diabetes Research, Department of Internal Medicine, Sahlgrenska University Hospital, Guldhetsgatan, Gothenburg S-413 45 Goteborg, Sweden. E-mail. ulf.smith{at}medic.gu.se
Thiazolidinediones (TZD) improve insulin sensitivity in human as well as
in different animal models of insulin resistance and Type 2 diabetes.
However, no clear link to the insulin signaling events has been
identified. Using differentiated 3T3-L1 adipocytes, we found that TZD
rapidly and markedly increased IRS-2 gene expression. This effect was
specific for PPAR
agonists and was not seen with PPAR
agonists.
It was rapidly induced (within 4 h) and maintained throughout the
observation period of 48 h. It was also concentration dependent
(EC50 
50 nM) and not inhibited by cycloheximide,
suggesting a direct effect on the IRS-2 promoter. There was no evidence
that TZD altered IRS-2 mRNA stability, supporting that the increased
mRNA levels were due to an increased gene transcription. IRS-2 protein
expression was increased 30% after 48 h and 50% after
96 h. No effects of TZD were seen on IRS-1, PKB/Akt, or GLUT4 gene
expression. TZD also increased IRS-2 mRNA levels in cultured human
adipose tissue. These data show the first direct link between TZD and a
critical molecule in insulin’s signaling cascade in both 3T3-L1 and
human adipocytes, and indicate a novel mode of action of these
compounds.—Smith, U., Gogg, S., Johansson, A., Olausson, T., Rotter,
V., Svalstedt, B. Thiazolidinediones (PPAR agonists) but not PPAR
agonists increase IRS-2 gene expression in 3T3-L1 and human adipocytes.
Key Words: insulin signaling • insulin action • gene transcription • IRS-2 • PPAR
This article has been cited by other articles:
|
|
 |
|
  J. Sevillano, J. de Castro, C. Bocos, E. Herrera, and M. P. Ramos Role of Insulin Receptor Substrate-1 Serine 307 Phosphorylation and Adiponectin in Adipose Tissue Insulin Resistance in Late Pregnancy Endocrinology, December 1, 2007; 148(12): 5933 - 5942. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Murdolo, A. Hammarstedt, M. Sandqvist, M. Schmelz, C. Herder, U. Smith, and P.-A. Jansson Monocyte Chemoattractant Protein-1 in Subcutaneous Abdominal Adipose Tissue: Characterization of Interstitial Concentration and Regulation of Gene Expression by Insulin J. Clin. Endocrinol. Metab., July 1, 2007; 92(7): 2688 - 2695. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. C. Reddy, Y. Hao, S.-H. Lee, S. R. Gangireddy, C. Owyang, and M. J. DiMagno Pioglitazone reverses insulin resistance and impaired CCK-stimulated pancreatic secretion in eNOS(-/-) mice: therapy for exocrine pancreatic disorders? Am J Physiol Gastrointest Liver Physiol, July 1, 2007; 293(1): G112 - G120. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F Sentinelli, E Filippi, M G Cavallo, S Romeo, M Fanelli, and M G Baroni The G972R variant of the insulin receptor substrate-1 gene impairs insulin signaling and cell differentiation in 3T3L1 adipocytes; treatment with a PPAR{gamma} agonist restores normal cell signaling and differentiation J. Endocrinol., February 1, 2006; 188(2): 271 - 285. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. S. Gardner, B. J. Dewar, and L. M. Graves Activation of Mitogen-Activated Protein Kinases by Peroxisome Proliferator-Activated Receptor Ligands: An Example of Nongenomic Signaling Mol. Pharmacol., October 1, 2005; 68(4): 933 - 941. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. K.R. Karlsson, K. Hallsten, M. Bjornholm, H. Tsuchida, A. V. Chibalin, K. A. Virtanen, O. J. Heinonen, F. Lonnqvist, P. Nuutila, and J. R. Zierath Effects of Metformin and Rosiglitazone Treatment on Insulin Signaling and Glucose Uptake in Patients With Newly Diagnosed Type 2 Diabetes: A Randomized Controlled Study Diabetes, May 1, 2005; 54(5): 1459 - 1467. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 U. Kintscher and R. E. Law PPAR{gamma}-mediated insulin sensitization: the importance of fat versus muscle Am J Physiol Endocrinol Metab, February 1, 2005; 288(2): E287 - E291. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Yki-Jarvinen Thiazolidinediones N. Engl. J. Med., September 9, 2004; 351(11): 1106 - 1118. [Full Text] [PDF]
|
|
|
|
 |
|
 S. C. Benson, H. A. Pershadsingh, C. I. Ho, A. Chittiboyina, P. Desai, M. Pravenec, N. Qi, J. Wang, M. A. Avery, and T. W. Kurtz Identification of Telmisartan as a Unique Angiotensin II Receptor Antagonist With Selective PPAR{gamma}-Modulating Activity Hypertension, May 1, 2004; 43(5): 993 - 1002. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H.-i. Kim and Y.-h. Ahn Role of Peroxisome Proliferator-Activated Receptor-{gamma} in the Glucose-Sensing Apparatus of Liver and {beta}-Cells Diabetes, February 1, 2004; 53(90001): S60 - 65. [Abstract] [Full Text]
|
|
|
|
 |
|
 V. Rotter, I. Nagaev, and U. Smith Interleukin-6 (IL-6) Induces Insulin Resistance in 3T3-L1 Adipocytes and Is, Like IL-8 and Tumor Necrosis Factor-{alpha}, Overexpressed in Human Fat Cells from Insulin-resistant Subjects J. Biol. Chem., November 14, 2003; 278(46): 45777 - 45784. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. M. Meyer, K. Levin, T. Grimmsmann, N. Perwitz, A. Eirich, H. Beck-Nielsen, and H. H. Klein Troglitazone Treatment Increases Protein Kinase B Phosphorylation in Skeletal Muscle of Normoglycemic Subjects at Risk for the Development of Type 2 Diabetes Diabetes, September 1, 2002; 51(9): 2691 - 2697. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Jiang, Q. Dallas-Yang, Z. Li, D. Szalkowski, F. Liu, X. Shen, M. Wu, G. Zhou, T. Doebber, J. Berger, et al. Potentiation of Insulin Signaling in Tissues of Zucker Obese Rats After Acute and Long-Term Treatment With PPAR{gamma} Agonists Diabetes, August 1, 2002; 51(8): 2412 - 2419. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Tamori, J. Masugi, N. Nishino, and M. Kasuga Role of Peroxisome Proliferator-Activated Receptor-{gamma} in Maintenance of the Characteristics of Mature 3T3-L1 Adipocytes Diabetes, July 1, 2002; 51(7): 2045 - 2055. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Walczak and P. Tontonoz PPARadigms and PPARadoxes: expanding roles for PPAR{gamma} in the control of lipid metabolism J. Lipid Res., February 1, 2002; 43(2): 177 - 186. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y.-B. Kim, T. P. Ciaraldi, A. Kong, D. Kim, N. Chu, P. Mohideen, S. Mudaliar, R. R. Henry, and B. B. Kahn Troglitazone but not Metformin Restores Insulin-Stimulated Phosphoinositide 3-Kinase Activity and Increases p110{beta} Protein Levels in Skeletal Muscle of Type 2 Diabetic Subjects Diabetes, February 1, 2002; 51(2): 443 - 448. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
