| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
1 Garvan Institute of Medical Research, Sydney, New South Wales 2010, Australia; and 2 Diabetes and Metabolism Unit, Boston University Medical Center, Boston, Massachusetts 02118
Chronic glucose
infusion results in hyperinsulinemia and causes lipid accumulation and
insulin resistance in rat muscle. To examine possible mechanisms for
the insulin resistance, alterations in malonyl-CoA and long-chain
acyl-CoA (LCA-CoA) concentration and the distribution of protein kinase
C (PKC) isozymes, putative links between muscle lipids and insulin
resistance, were determined. Cannulated rats were infused
with glucose (40 mg · kg
1 · min1)
for 1 or 4 days. This increased red quadriceps muscle LCA-CoA content
(sum of 6 species) by 1.3-fold at 1 day and 1.4-fold at 4 days vs.
saline-infused controls (both P < 0.001 vs. control). The concentration of malonyl-CoA was also increased
(1.7-fold at 1 day, P < 0.01, and
2.2-fold at 4 days, P < 0.001 vs.
control), suggesting an even greater increase in cytosolic LCA-CoA. The ratio of membrane to cytosolic PKC-
was increased twofold in the red
gastrocnemius after both 1 and 4 days, suggesting chronic activation.
No changes were observed for PKC-
, -
, and -
. We conclude that
LCA-CoAs accumulate in muscle during chronic glucose infusion,
consistent with a malonyl-CoA-induced inhibition of fatty acid
oxidation (reverse glucose-fatty acid cycle). Accumulation of LCA-CoAs
could play a role in the generation of muscle insulin resistance by
glucose oversupply, either directly or via chronic activation of
PKC-.
hyperglycemia; hyperinsulinemia; malonyl-CoA; long-chain acyl-CoA
This article has been cited by other articles:
|
|
 |
|
  A. J. Hoy, A. E. Brandon, N. Turner, M. J. Watt, C. R. Bruce, G. J. Cooney, and E. W. Kraegen Lipid and insulin infusion-induced skeletal muscle insulin resistance is likely due to metabolic feedback and not changes in IRS-1, Akt, or AS160 phosphorylation Am J Physiol Endocrinol Metab, July 1, 2009; 297(1): E67 - E75. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E.-G. Hong, D. Y. Jung, H. J. Ko, Z. Zhang, Z. Ma, J. Y. Jun, J. H. Kim, A. D. Sumner, T. C. Vary, T. W. Gardner, et al. Nonobese, insulin-deficient Ins2Akita mice develop type 2 diabetes phenotypes including insulin resistance and cardiac remodeling Am J Physiol Endocrinol Metab, December 1, 2007; 293(6): E1687 - E1696. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. J. Hoy, C. R. Bruce, A. Cederberg, N. Turner, D. E. James, G. J. Cooney, and E. W. Kraegen Glucose infusion causes insulin resistance in skeletal muscle of rats without changes in Akt and AS160 phosphorylation Am J Physiol Endocrinol Metab, November 1, 2007; 293(5): E1358 - E1364. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y.-R. Cho, H.-J. Kim, S.-Y. Park, H. J. Ko, E.-G. Hong, T. Higashimori, Z. Zhang, D. Y. Jung, M. S. Ola, K. F. LaNoue, et al. Hyperglycemia, maturity-onset obesity, and insulin resistance in NONcNZO10/LtJ males, a new mouse model of type 2 diabetes Am J Physiol Endocrinol Metab, July 1, 2007; 293(1): E327 - E336. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J.-J. Park, J. R. Berggren, M. W. Hulver, J. A Houmard, and E. P. Hoffman GRB14, GPD1, and GDF8 as potential network collaborators in weight loss-induced improvements in insulin action in human skeletal muscle Physiol Genomics, October 11, 2006; 27(2): 114 - 121. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. J. Nadeau, L. B. Ehlers, L. E. Aguirre, R. L. Moore, K. N. Jew, H. K. Ortmeyer, B. C. Hansen, J. E. B. Reusch, and B. Draznin Exercise training and calorie restriction increase SREBP-1 expression and intramuscular triglyceride in skeletal muscle Am J Physiol Endocrinol Metab, July 1, 2006; 291(1): E90 - E98. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. E. Kuhl, N. B. Ruderman, N. Musi, L. J. Goodyear, M. E. Patti, S. Crunkhorn, D. Dronamraju, A. Thorell, J. Nygren, O. Ljungkvist, et al. Exercise training decreases the concentration of malonyl-CoA and increases the expression and activity of malonyl-CoA decarboxylase in human muscle Am J Physiol Endocrinol Metab, June 1, 2006; 290(6): E1296 - E1303. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. W. Kraegen, A. K. Saha, E. Preston, D. Wilks, A. J. Hoy, G. J. Cooney, and N. B. Ruderman Increased malonyl-CoA and diacylglycerol content and reduced AMPK activity accompany insulin resistance induced by glucose infusion in muscle and liver of rats Am J Physiol Endocrinol Metab, March 1, 2006; 290(3): E471 - E479. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Kiens Skeletal Muscle Lipid Metabolism in Exercise and Insulin Resistance Physiol Rev, January 1, 2006; 86(1): 205 - 243. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. B. Taylor, W. J. Ellingson, J. D. Lamb, D. G. Chesser, and W. W. Winder Long-chain acyl-CoA esters inhibit phosphorylation of AMP-activated protein kinase at threonine-172 by LKB1/STRAD/MO25 Am J Physiol Endocrinol Metab, June 1, 2005; 288(6): E1055 - E1061. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. A. Buhagiar, P. S. Hansen, B. Y. Kong, R. J. Clarke, C. Fernandes, and H. H. Rasmussen Dietary cholesterol alters Na+/K+ selectivity at intracellular Na+/K+ pump sites in cardiac myocytes Am J Physiol Cell Physiol, February 1, 2004; 286(2): C398 - C405. [Abstract] [Full Text]
|
|
|
|
|
|
D.-H. Han, M. M. Chen, and J. O. Holloszy Glucosamine and glucose induce insulin resistance by different mechanisms in rat skeletal muscle Am J Physiol Endocrinol Metab, December 1, 2003; 285(6): E1267 - E1272. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. A. Haber, T. K. T. Lam, Z. Yu, N. Gupta, T. Goh, E. Bogdanovic, A. Giacca, and I. G. Fantus N-acetylcysteine and taurine prevent hyperglycemia-induced insulin resistance in vivo: possible role of oxidative stress Am J Physiol Endocrinol Metab, October 1, 2003; 285(4): E744 - E753. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Yu, Y. Chen, G. W. Cline, D. Zhang, H. Zong, Y. Wang, R. Bergeron, J. K. Kim, S. W. Cushman, G. J. Cooney, et al. Mechanism by Which Fatty Acids Inhibit Insulin Activation of Insulin Receptor Substrate-1 (IRS-1)-associated Phosphatidylinositol 3-Kinase Activity in Muscle J. Biol. Chem., December 20, 2002; 277(52): 50230 - 50236. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Lin, M. J. Brady, K. Wolanske, R. Holbert, N. B. Ruderman, and G. C. Yaney Alterations of nPKC distribution, but normal Akt/PKB activation in denervated rat soleus muscle Am J Physiol Endocrinol Metab, August 1, 2002; 283(2): E318 - E325. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. D. Hegarty, G. J. Cooney, E. W. Kraegen, and S. M. Furler Increased Efficiency of Fatty Acid Uptake Contributes to Lipid Accumulation in Skeletal Muscle of High Fat-Fed Insulin-Resistant Rats Diabetes, May 1, 2002; 51(5): 1477 - 1484. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Taegtmeyer, P. McNulty, and M. E. Young Adaptation and Maladaptation of the Heart in Diabetes: Part I: General Concepts Circulation, April 9, 2002; 105(14): 1727 - 1733. [Full Text] [PDF]
|
|
|
|
|
|
A. B. Mayerson, R. S. Hundal, S. Dufour, V. Lebon, D. Befroy, G. W. Cline, S. Enocksson, S. E. Inzucchi, G. I. Shulman, and K. F. Petersen The Effects of Rosiglitazone on Insulin Sensitivity, Lipolysis, and Hepatic and Skeletal Muscle Triglyceride Content in Patients With Type 2 Diabetes Diabetes, March 1, 2002; 51(3): 797 - 802. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Franch, J. Knudsen, B. A. Ellis, P. K. Pedersen, G. J. Cooney, and J. Jensen Acyl-CoA Binding Protein Expression Is Fiber Type- Specific and Elevated in Muscles From the Obese Insulin-Resistant Zucker Rat Diabetes, February 1, 2002; 51(2): 449 - 454. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. D. McGarry Banting Lecture 2001: Dysregulation of Fatty Acid Metabolism in the Etiology of Type 2 Diabetes Diabetes, January 1, 2002; 51(1): 7 - 18. [Full Text] [PDF]
|
|
|
|
|
|
Y. Lin, S. I. Itani, T. G. Kurowski, D. J. Dean, Z. Luo, G. C. Yaney, and N. B. Ruderman Inhibition of insulin signaling and glycogen synthesis by phorbol dibutyrate in rat skeletal muscle Am J Physiol Endocrinol Metab, July 1, 2001; 281(1): E8 - E15. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. E. Young, G. W. Goodwin, J. Ying, P. Guthrie, C. R. Wilson, F. A. Laws, and H. Taegtmeyer Regulation of cardiac and skeletal muscle malonyl-CoA decarboxylase by fatty acids Am J Physiol Endocrinol Metab, March 1, 2001; 280(3): E471 - E479. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-M. Ye, P. J. Doyle, M. A. Iglesias, D. G. Watson, G. J. Cooney, and E. W. Kraegen Peroxisome Proliferator--Activated Receptor (PPAR)-{alpha} Activation Lowers Muscle Lipids and Improves Insulin Sensitivity in High Fat--Fed Rats: Comparison With PPAR-{gamma} Activation Diabetes, February 1, 2001; 50(2): 411 - 417. [Abstract] [Full Text]
|
|
|
|
|
|
K. Kawanaka, D.-H. Han, J. Gao, L. A. Nolte, and J. O. Holloszy Development of Glucose-induced Insulin Resistance in Muscle Requires Protein Synthesis J. Biol. Chem., June 1, 2001; 276(23): 20101 - 20107. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
