Skeletal muscle plays an integral role in the regulation of the circulating glucose concentration. Thus, the mechanism for skeletal muscle insulin resistance is of great importance for the understanding of the pathogenesis of type-2 diabetes. While a great deal of research has been done on determining what causes skeletal muscle insulin resistance, the mechanism remains unclear. Recent work has suggested that reduced mitochondrial content and/or function in skeletal muscle contributes to insulin resistance and may in fact be genetically determined. It is our hypothesis that the reduction in muscle mitochondria is due to physical inactivity and plays no role in modulating muscle insulin resistance. The primary goal of this study determine the effect of a high fat diet that causes visceral obesity and insulin resistance on skeletal muscle content and functional mitochondria in rats. A second goal is to determine whether insulin stimulated phospohorylation of Akt substrate 160 is impaired in response to high fat feeding. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32DK076410-01
Application #
7155943
Study Section
Special Emphasis Panel (ZRG1-F06-J (20))
Program Officer
Hyde, James F
Project Start
2006-09-01
Project End
2008-08-31
Budget Start
2006-09-01
Budget End
2007-08-31
Support Year
1
Fiscal Year
2006
Total Cost
$45,976
Indirect Cost
Name
Washington University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Hancock, Chad R; Han, Dong-Ho; Higashida, Kazuhiko et al. (2011) Does calorie restriction induce mitochondrial biogenesis? A reevaluation. FASEB J 25:785-91
Hancock, Chad R; Han, Dong-Ho; Chen, May et al. (2008) High-fat diets cause insulin resistance despite an increase in muscle mitochondria. Proc Natl Acad Sci U S A 105:7815-20
Garcia-Roves, Pablo; Huss, Janice M; Han, Dong-Ho et al. (2007) Raising plasma fatty acid concentration induces increased biogenesis of mitochondria in skeletal muscle. Proc Natl Acad Sci U S A 104:10709-13
Geiger, Paige C; Hancock, Chad; Wright, David C et al. (2007) IL-6 increases muscle insulin sensitivity only at superphysiological levels. Am J Physiol Endocrinol Metab 292:E1842-6