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Science 21 January 2005:
Vol. 307. no. 5708, pp. 384 - 387
DOI: 10.1126/science.1104343
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Mitochondrial Dysfunction and Type 2 Diabetes

Bradford B. Lowell1 and Gerald I. Shulman2

Maintenance of normal blood glucose levels depends on a complex interplay between the insulin responsiveness of skeletal muscle and liver and glucose-stimulated insulin secretion by pancreatic ß cells. Defects in the former are responsible for insulin resistance, and defects in the latter are responsible for progression to hyperglycemia. Emerging evidence supports the potentially unifying hypothesis that both of these prominent features of type 2 diabetes are caused by mitochondrial dysfunction.

1 Department of Medicine, Beth Israel Deaconess Medical Center, 99 Brookline Avenue, Harvard Medical School, Boston, MA 02215, USA. E-mail: blowell{at}bidmc.harvard.edu
2 Howard Hughes Medical Institute, Department of Internal Medicine and Department of Cellular and Molecular Physiology, Yale University School of Medicine, 300 Cedar Street, New Haven, CT 06536, USA. E-mail: gerald.shulman{at}yale.edu

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Exposure to Chronic High Glucose Induces {beta}-Cell Apoptosis Through Decreased Interaction of Glucokinase With Mitochondria: Downregulation of Glucokinase in Pancreatic {beta}-Cells.
W.-H. Kim, J. W. Lee, Y. H. Suh, S. H. Hong, J. S. Choi, J. H. Lim, J. H. Song, B. Gao, and M. H. Jung (2005)
Diabetes 54, 2602-2611
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Mitochondria and Reactive Oxygen Species: An Evolution in Function.
D. D. Gutterman (2005)
Circ. Res. 97, 302-304
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Regulation of Blood Glucose by Hypothalamic Pyruvate Metabolism.
T. K. T. Lam, R. Gutierrez-Juarez, A. Pocai, and L. Rossetti (2005)
Science 309, 943-947
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Increasing dietary palmitic acid decreases fat oxidation and daily energy expenditure.
C L. Kien, J. Y Bunn, and F. Ugrasbul (2005)
Am. J. Clinical Nutrition 82, 320-326
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The Uncoupling Protein 2 Ala55Val Polymorphism Is Associated with Diabetes Mellitus: The CARDIA Study.
X. Yu, D. R. Jacobs Jr, P. J. Schreiner, M. D. Gross, M. W. Steffes, and M. Fornage (2005)
Clin. Chem. 51, 1451-1456
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Fine-Mapping Gene-by-Diet Interactions on Chromosome 13 in a LG/J x SM/J Murine Model of Obesity.
T. H. Ehrich, T. Hrbek, J. P. Kenney-Hunt, L. S. Pletscher, B. Wang, C. F. Semenkovich, and J. M. Cheverud (2005)
Diabetes 54, 1863-1872
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