|
 |
|
|||||||
|
|||||||||
Diabetes 51:3211-3219, 2002
© 2002 by the American Diabetes Association, Inc.
Uncoupling Protein 2 Knockout Mice Have Enhanced Insulin Secretory Capacity After a High-Fat Diet
1 Departments of Medicine and Physiology, University of Toronto, Ontario, Canada
2 Division of Endocrinology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts
3 Department of Anatomy and Physiology, Atlantic Veterinary College, University of Prince Edward Island, Prince Edward Island, Canada
Uncoupling protein 2 (UCP2) may act as an important regulator of insulin secretion. In this study, ß-cell function in UCP2-deficient mice was examined after a 45% high-fat diet (HFD) to assess its role during the development of diet-induced type 2 diabetes. HFD-fed UCP2 (-/-) mice have lower fasting blood glucose and elevated insulin levels when compared with wild-type (WT) mice. UCP2 (-/-) mice also have enhanced ß-cell glucose sensitivity compared with WT mice after HFD, a result that is due in part to the deterioration of glucose responsiveness in WT mice. HFD-fed UCP2 (-/-) mice have increased insulin secretory capacity as a result of increased pancreatic ß-cell mass and insulin content per islet. Islets from WT mice exposed to 0.5 mmol/l palmitate for 48 h have significantly reduced mitochondrial membrane potential, ATP concentrations, and glucose responsiveness compared with UCP2 (-/-) islets, suggesting that elevated UCP2 in WT mice increases proton leak and decreases mitochondrial ATP production. Highly increased carnitine palmitoyl transferase-1 gene expression in UCP2 (-/-) mice is suggestive of enhanced fatty acid oxidizing capacity, particularly after HFD stress. These results further establish UCP2 as a component in glucose sensing and suggest a possible new aspect of UCP2 function during the progression of type 2 diabetes.
CiteULike 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  J. D. Wikstrom, S. M. Katzman, H. Mohamed, G. Twig, S. A. Graf, E. Heart, A. J.A. Molina, B. E. Corkey, L. M. de Vargas, N. N. Danial, et al. {beta}-Cell Mitochondria Exhibit Membrane Potential Heterogeneity That Can Be Altered by Stimulatory or Toxic Fuel Levels Diabetes, October 1, 2007; 56(10): 2569 - 2578. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. S. Olofsson, S. Collins, M. Bengtsson, L. Eliasson, A. Salehi, K. Shimomura, A. Tarasov, C. Holm, F. Ashcroft, and P. Rorsman Long-Term Exposure to Glucose and Lipids Inhibits Glucose-Induced Insulin Secretion Downstream of Granule Fusion With Plasma Membrane Diabetes, July 1, 2007; 56(7): 1888 - 1897. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Chevillotte, M. Giralt, B. Miroux, D. Ricquier, and F. Villarroya Uncoupling Protein-2 Controls Adiponectin Gene Expression in Adipose Tissue Through the Modulation of Reactive Oxygen Species Production Diabetes, April 1, 2007; 56(4): 1042 - 1050. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. T. De Souza, E. P. Araujo, L. F. Stoppiglia, J. R. Pauli, E. Ropelle, S. A. Rocco, R. M. Marin, K. G. Franchini, J. B. Carvalheira, M. J. Saad, et al. Inhibition of UCP2 expression reverses diet-induced diabetes mellitus by effects on both insulin secretion and action FASEB J, April 1, 2007; 21(4): 1153 - 1163. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Nakano, Y. Inada, H. Masuzaki, T. Tanaka, S. Yasue, T. Ishii, N. Arai, K. Ebihara, K. Hosoda, K. Maruyama, et al. Bezafibrate regulates the expression and enzyme activity of 11beta-hydroxysteroid dehydrogenase type 1 in murine adipose tissue and 3T3-L1 adipocytes Am J Physiol Endocrinol Metab, April 1, 2007; 292(4): E1213 - E1222. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Kashemsant and C. B Chan Impact of uncoupling protein-2 overexpression on proinsulin processing J. Mol. Endocrinol., December 1, 2006; 37(3): 517 - 526. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. C Saleh, M. B Wheeler, and C. B Chan Endogenous islet uncoupling protein-2 expression and loss of glucose homeostasis in ob/ob mice. J. Endocrinol., September 1, 2006; 190(3): 659 - 667. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T S McQuaid, M C Saleh, J W Joseph, A Gyulkhandanyan, J E Manning-Fox, J D MacLellan, M B Wheeler, and C B Chan cAMP-mediated signaling normalizes glucose-stimulated insulin secretion in uncoupling protein-2 overexpressing {beta}-cells. J. Endocrinol., September 1, 2006; 190(3): 669 - 680. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K.-T. T. Nguyen, P. Tajmir, C. H. Lin, N. Liadis, X.-D. Zhu, M. Eweida, G. Tolasa-Karaman, F. Cai, R. Wang, T. Kitamura, et al. Essential Role of Pten in Body Size Determination and Pancreatic {beta}-Cell Homeostasis In Vivo Mol. Cell. Biol., June 15, 2006; 26(12): 4511 - 4518. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Sanchez-Blanco, Y.-W. C. Fridell, and S. L. Helfand Involvement of Drosophila Uncoupling Protein 5 in Metabolism and Aging Genetics, March 1, 2006; 172(3): 1699 - 1710. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Oberkofler, K. Klein, T. K. Felder, F. Krempler, and W. Patsch Role of Peroxisome Proliferator-Activated Receptor-{gamma} Coactivator-1{alpha} in the Transcriptional Regulation of the Human Uncoupling Protein 2 Gene in INS-1E Cells Endocrinology, February 1, 2006; 147(2): 966 - 976. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Toyoshima, O. Gavrilova, S. Yakar, W. Jou, S. Pack, Z. Asghar, M. B. Wheeler, and D. LeRoith Leptin Improves Insulin Resistance and Hyperglycemia in a Mouse Model of Type 2 Diabetes Endocrinology, September 1, 2005; 146(9): 4024 - 4035. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Wang, G. Kouri, and C. B. Wollheim ER stress and SREBP-1 activation are implicated in {beta}-cell glucolipotoxicity J. Cell Sci., September 1, 2005; 118(17): 3905 - 3915. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Yu, D. R. Jacobs Jr, P. J. Schreiner, M. D. Gross, M. W. Steffes, and M. Fornage The Uncoupling Protein 2 Ala55Val Polymorphism Is Associated with Diabetes Mellitus: The CARDIA Study Clin. Chem., August 1, 2005; 51(8): 1451 - 1456. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. W. Fariss, C. B. Chan, M. Patel, B. Van Houten, and S. Orrenius ROLE of MITOCHONDRIA in TOXIC OXIDATIVE STRESS Mol. Interv., April 1, 2005; 5(2): 94 - 111. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. B. Lowell and G. I. Shulman Mitochondrial Dysfunction and Type 2 Diabetes Science, January 21, 2005; 307(5708): 384 - 387. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. W. Joseph, V. Koshkin, M. C. Saleh, W. I. Sivitz, C.-Y. Zhang, B. B. Lowell, C. B. Chan, and M. B. Wheeler Free Fatty Acid-induced {beta}-Cell Defects Are Dependent on Uncoupling Protein 2 Expression J. Biol. Chem., December 3, 2004; 279(49): 51049 - 51056. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. S. Remedi, Joseph. C. Koster, K. Markova, S. Seino, T. Miki, B. L. Patton, M. L. McDaniel, and C. G. Nichols Diet-Induced Glucose Intolerance in Mice With Decreased {beta}-Cell ATP-Sensitive K+ Channels Diabetes, December 1, 2004; 53(12): 3159 - 3167. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Heron-Milhavet, M. Haluzik, S. Yakar, O. Gavrilova, S. Pack, W. C. Jou, A. Ibrahimi, H. Kim, D. Hunt, D. Yau, et al. Muscle-Specific Overexpression of CD36 Reverses the Insulin Resistance and Diabetes of MKR Mice Endocrinology, October 1, 2004; 145(10): 4667 - 4676. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. E. MacDonald, J. W. Joseph, D. Yau, J. Diao, Z. Asghar, F. Dai, G. Y. Oudit, M. M. Patel, P. H. Backx, and M. B. Wheeler Impaired Glucose-Stimulated Insulin Secretion, Enhanced Intraperitoneal Insulin Tolerance, and Increased {beta}-Cell Mass in Mice Lacking the p110{gamma} Isoform of Phosphoinositide 3-Kinase Endocrinology, September 1, 2004; 145(9): 4078 - 4083. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Poitout {beta}-Cell Lipotoxicity: Burning Fat into Heat? Endocrinology, August 1, 2004; 145(8): 3563 - 3565. [Full Text] [PDF]
|
|
|
|
|
|
T. Yamashita, K. Eto, Y. Okazaki, S. Yamashita, T. Yamauchi, N. Sekine, R. Nagai, M. Noda, and T. Kadowaki Role of Uncoupling Protein-2 Up-Regulation and Triglyceride Accumulation in Impaired Glucose-Stimulated Insulin Secretion in a {beta}-Cell Lipotoxicity Model Overexpressing Sterol Regulatory Element-Binding Protein-1c Endocrinology, August 1, 2004; 145(8): 3566 - 3577. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. D'Adamo, L. Perego, M. Cardellini, M. A. Marini, S. Frontoni, F. Andreozzi, A. Sciacqua, D. Lauro, P. Sbraccia, M. Federici, et al. The -866A/A Genotype in the Promoter of the Human Uncoupling Protein 2 Gene Is Associated With Insulin Resistance and Increased Risk of Type 2 Diabetes Diabetes, July 1, 2004; 53(7): 1905 - 1910. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Ashcroft and P. Rorsman Type 2 diabetes mellitus: not quite exciting enough? Hum. Mol. Genet., April 1, 2004; 13(suppl_1): R21 - R31. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Sasahara, M. Nishi, H. Kawashima, K. Ueda, S. Sakagashira, H. Furuta, E. Matsumoto, T. Hanabusa, H. Sasaki, and K. Nanjo Uncoupling Protein 2 Promoter Polymorphism -866G/A Affects Its Expression in {beta}-Cells and Modulates Clinical Profiles of Japanese Type 2 Diabetic Patients Diabetes, February 1, 2004; 53(2): 482 - 485. [Abstract] [Full Text]
|
|
|
|
|
|
C. B. Chan, M. C. Saleh, V. Koshkin, and M. B. Wheeler Uncoupling Protein 2 and Islet Function Diabetes, February 1, 2004; 53(90001): S136 - 142. [Abstract] [Full Text]
|
|
|
|
 |
|
 Y. Teshima, M. Akao, S. P. Jones, and E. Marban Uncoupling Protein-2 Overexpression Inhibits Mitochondrial Death Pathway in Cardiomyocytes Circ. Res., August 8, 2003; 93(3): 192 - 200. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Kim, M. Haluzik, Z. Asghar, D. Yau, J. W. Joseph, A. M. Fernandez, M. L. Reitman, S. Yakar, B. Stannard, L. Heron-Milhavet, et al. Peroxisome Proliferator-Activated Receptor-{alpha} Agonist Treatment in a Transgenic Model of Type 2 Diabetes Reverses the Lipotoxic State and Improves Glucose Homeostasis Diabetes, July 1, 2003; 52(7): 1770 - 1778. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Koshkin, X. Wang, P. E. Scherer, C. B. Chan, and M. B. Wheeler Mitochondrial Functional State in Clonal Pancreatic {beta}-Cells Exposed to Free Fatty Acids J. Biol. Chem., May 23, 2003; 278(22): 19709 - 19715. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Diabetes | Diabetes Care | Clinical Diabetes | Diabetes Spectrum |