| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Department of Physiology and Biophysics, University of Southern California Keck School of Medicine, Los Angeles, California, USA
* To whom correspondence should be addressed. E-mail: youn{at}usc.edu.
Starvation and experimental diabetes induce a stable increase in pyruvate dehydrogenase kinase (PDK) activity in skeletal muscle, which is largely due to a selective upregulation of PDK4 expression. Increased free fatty acid (FFA) level has been suggested to be responsible for the upregulation. Since these metabolic states are also characterized by insulin deficiency, the present study was designed to examine whether insulin has a significant effect to regulate PDK mRNA expression in rat skeletal muscle. In Study 1 overnight fasted rats received an infusion of saline or insulin for 5 hours (n=6 for each). During the insulin infusion, plasma glucose was clamped at basal levels (euglycemic hyperinsulinemic clamp). A third group (n=6) received Intralipid infusion during the clamp to prevent a fall in plasma FFA. PDK2 mRNA level in gastrocnemius muscle was not altered by insulin or FFA (i.e., Intralipid infusion). In contrast, PDK4 mRNA level was decreased 72% by insulin (P<0.05), and Intralipid infusion prevented only 20% of the decrease. PDK4 protein level was decreased ~20% by insulin (P<0.05) but this effect was not altered by Intralipid infusion. In Study 2 overnight fasted rats were refed or received an infusion of saline or nicotinic acid (NA, 30 µmol/h) for 5 hours (n=5 for each). During the refeeding and the NA infusion, plasma FFA levels were similarly (i.e., 60-70% vs. saline control) lowered. Muscle PDK4 mRNA level decreased 77% after the refeeding (P<0.05) but not after the NA infusion. In conclusion, the present data indicate that insulin had a profound effect to suppress PDK4 expression in skeletal muscle and that, in contrary to previous suggestions, circulating FFA had little impact on PDK4 mRNA expression, at least within 5 hours.
This article has been cited by other articles:
|
|
 |
|
  C. M. Schummer, U. Werner, N. Tennagels, D. Schmoll, G. Haschke, H.-P. Juretschke, M. S. Patel, M. Gerl, W. Kramer, and A. W. Herling Dysregulated pyruvate dehydrogenase complex in Zucker diabetic fatty rats Am J Physiol Endocrinol Metab, January 1, 2008; 294(1): E88 - E96. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 U. A. White, A. A. Coulter, T. K. Miles, and J. M. Stephens The STAT5A-Mediated Induction of Pyruvate Dehydrogenase Kinase 4 Expression by Prolactin or Growth Hormone in Adipocytes Diabetes, June 1, 2007; 56(6): 1623 - 1629. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. I. Kim, F. N. Lee, W. S. Choi, S. Lee, and J. H. Youn Insulin Regulation of Skeletal Muscle PDK4 mRNA Expression Is Impaired in Acute Insulin-Resistant States. Diabetes, August 1, 2006; 55(8): 2311 - 2317. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. E. Civitarese, M. K. C. Hesselink, A. P. Russell, E. Ravussin, and P. Schrauwen Glucose ingestion during exercise blunts exercise-induced gene expression of skeletal muscle fat oxidative genes Am J Physiol Endocrinol Metab, December 1, 2005; 289(6): E1023 - E1029. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. J. Cluberton, S. L. McGee, R. M. Murphy, and M. Hargreaves Effect of carbohydrate ingestion on exercise-induced alterations in metabolic gene expression J Appl Physiol, October 1, 2005; 99(4): 1359 - 1363. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. S. Golfman, C. R. Wilson, S. Sharma, M. Burgmaier, M. E. Young, P. H. Guthrie, M. Van Arsdall, J. V. Adrogue, K. K. Brown, and H. Taegtmeyer Activation of PPAR{gamma} enhances myocardial glucose oxidation and improves contractile function in isolated working hearts of ZDF rats Am J Physiol Endocrinol Metab, August 1, 2005; 289(2): E328 - E336. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. A. Turvey, G. J. F. Heigenhauser, M. Parolin, and S. J. Peters Elevated n-3 fatty acids in a high-fat diet attenuate the increase in PDH kinase activity but not PDH activity in human skeletal muscle J Appl Physiol, January 1, 2005; 98(1): 350 - 355. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. A. Turvey, G. J. F. Heigenhauser, M. Parolin, and S. J. Peters Elevated n-3 fatty acids in a high-fat diet attenuate the increase in PDH kinase activity but not PDH activity in human skeletal muscle J Appl Physiol, January 1, 2005; 98(1): 350 - 355. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
