Malonyl coenzyme A and the regulation of functional carnitine palmitoyltransferase-1 activity and fat oxidation in human skeletal muscle.
作者： Douglas Paddon-Jones , Elena Volpi , Blake B. Rasmussen , Robert R. Wolfe , Ulf C. Holmbäck
DOI: 10.1172/JCI15715
关键词:
摘要: Physiological hyperglycemia with hyperinsulinemia reduces fat oxidation in skeletal muscle. The mechanism responsible for this decrease human muscle is not known and may contribute to the development of insulin resistance. We hypothesized that transfer long-chain fatty acids (LCFAs) into mitochondria via carnitine palmitoyltransferase-1 (CPT-1) inhibited by increased malonyl coenzyme A (malonyl-CoA) (a potent inhibitor CPT-1) during hyperinsulinemia. studied six healthy subjects after an overnight fast induced 5-hour period Muscle acid was calculated using stable isotope methodology combined blood sampling from femoral artery vein one leg. functional CPT-1 activity assessed concurrently infusing LCFA tracer a CPT-independent medium-chain tracer. biopsies were obtained vastus lateralis periods fasting Hyperglycemia decreased oxidation, but had no effect on uptake or across Malonyl-CoA concentration significantly 0.13 ± 0.01 0.35 0.07 nmol/g conclude increases malonyl-CoA, inhibits activity, shunts away toward storage
utsystem.edu参考文章(45)
Demetrios Vavvas, Alexios Apazidis, Asish K. Saha, James Gamble, Abhay Patel, Bruce E. Kemp, Lee A. Witters, Neil B. Ruderman, Contraction-induced Changes in Acetyl-CoA Carboxylase and 5′-AMP-activated Kinase in Skeletal Muscle Journal of Biological Chemistry. ,vol. 272, pp. 13255- 13261 ,(1997) , 10.1074/JBC.272.20.13255
L. Abu-Elheiga, W. R. Brinkley, L. Zhong, S. S. Chirala, G. Woldegiorgis, S. J. Wakil, The subcellular localization of acetyl-CoA carboxylase 2. Proceedings of the National Academy of Sciences of the United States of America. ,vol. 97, pp. 1444- 1449 ,(2000) , 10.1073/PNAS.97.4.1444
Lutfi Abu-Elheiga, Martin M Matzuk, Khaled AH Abo-Hashema, Salih J Wakil, Continuous Fatty Acid Oxidation and Reduced Fat Storage in Mice Lacking Acetyl-CoA Carboxylase 2 Science. ,vol. 291, pp. 2613- 2616 ,(2001) , 10.1126/SCIENCE.1056843
J. McGarry, What if Minkowski had been ageusic? An alternative angle on diabetes. Science. ,vol. 258, pp. 766- 770 ,(1992) , 10.1126/SCIENCE.1439783
WILLLAM W. WINDER, Malonyl-CoA--regulator of fatty acid oxidation in muscle during exercise. Exercise and Sport Sciences Reviews. ,vol. 26, pp. 117- 132 ,(1998) , 10.1249/00003677-199800260-00007
M. R. Murti, B. Grietens, C. Van Hoof, G. Borghs, 1.7–1.9 μm InxGa1−xAs/InyAl1−yAs light‐emitting diodes lattice‐mismatched grown on GaAs Journal of Applied Physics. ,vol. 78, pp. 578- 580 ,(1995) , 10.1063/1.360574
D. E. Kelley, B. H. Goodpaster, Skeletal muscle triglyceride. An aspect of regional adiposity and insulin resistance. Diabetes Care. ,vol. 24, pp. 933- 941 ,(2001) , 10.2337/DIACARE.24.5.933
Nobuharu Fujii, Tatsuya Hayashi, Michael F. Hirshman, Jeremy T. Smith, Susan A. Habinowski, Lennart Kaijser, James Mu, Olle Ljungqvist, Morris J. Birnbaum, Lee A. Witters, Anders Thorell, Laurie J. Goodyear, Exercise induces isoform-specific increase in 5'AMP-activated protein kinase activity in human skeletal muscle. Biochemical and Biophysical Research Communications. ,vol. 273, pp. 1150- 1155 ,(2000) , 10.1006/BBRC.2000.3073
I. Sakata, M. Yamanaka, Y. Hayashi, Properties of hydrogenated amorphous silicon prepared by alternatively repeating chemical-vapor deposition from disilane and hydrogen plasma treatment Journal of Applied Physics. ,vol. 74, pp. 2543- 2549 ,(1993) , 10.1063/1.354695
D. Ross Laybutt, Carsten Schmitz-Peiffer, Asish K. Saha, Neil B. Ruderman, Trevor J. Biden, Edward W. Kraegen, Muscle lipid accumulation and protein kinase C activation in the insulin-resistant chronically glucose-infused rat American Journal of Physiology-endocrinology and Metabolism. ,vol. 277, ,(1999) , 10.1152/AJPENDO.1999.277.6.E1070