Diabetes, Vol 46, Issue 3 348-353, Copyright © 1997 by American Diabetes Association

ARTICLES

Improved insulin sensitivity by bezafibrate in rats: relationship to fatty acid composition of skeletal-muscle triglycerides

H Matsui, K Okumura, K Kawakami, M Hibino, Y Toki and T Ito
Internal Medicine II, Nagoya University School of Medicine, Japan.

We investigated the effect of the lipid-lowering agent, bezafibrate, on insulin sensitivity in a dietary model of insulin resistance. Male Sprague-Dawley rats were divided into four groups: control group, administered a standard diet; high-fructose group, given a 40% fructose diet; high-fructose plus lard group, given a 40% fructose diet with 7% lard; and bezafibrate group, given a 40% fructose plus 7% lard diet with 10 mg x kg-1 x day-1 of oral bezafibrate. Insulin action was assessed after 2 weeks with a steady-state plasma glucose (SSPG) level. The fatty acid (FA) composition of skeletal-muscle triglycerides was also determined. A higher SSPG level (20.9 +/- 0.9 vs. 16.5 +/- 1.1 mmol/l in the control group, P < 0.05) as well as a higher systolic blood pressure (120 +/- 2 vs. 101 +/- 2 mmHg, P < 0.01) was observed in the high-fructose plus lard group, but not in the high-fructose group. These changes were prevented by bezafibrate administration. The FA composition of skeletal-muscle triglycerides demonstrated a higher percentage of saturated and monounsaturated FAs (P < 0.01) and a lower percentage of polyunsaturated FAs (P <0.01) in the high-fructose plus lard group versus the control group. These changes were consistent with differences in the dietary intake of FAs. Bezafibrate virtually normalized the FA composition in the high-fructose plus lard group. The ratio of C20:4 to C20:3, an index of delta5 desaturase activity, was significantly higher in the bezafibrate group versus the high-fructose plus lard group (8.60 +/- 0.76 vs. 2.04 +/- 0.27, P < 0.01). In conclusion, the dietary FA composition was closely related to insulin resistance in rats fed 40% fructose. Bezafibrate increased delta5 desaturase activity. Such action may contribute to the improvement of insulin sensitivity.
CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				R. Bergeron, J. Yao, J. W. Woods, E. I. Zycband, C. Liu, Z. Li, A. Adams, J. P. Berger, B. B. Zhang, D. E. Moller, et al. Peroxisome Proliferator-Activated Receptor (PPAR)-{alpha} Agonism Prevents the Onset of Type 2 Diabetes in Zucker Diabetic Fatty Rats: A Comparison with PPAR{gamma} Agonism Endocrinology, September 1, 2006; 147(9): 4252 - 4262. [Abstract] [Full Text] [PDF]

				A. T. De Souza, P. D. Cornwell, X. Dai, M. J. Caguyong, and R. G. Ulrich Agonists of the Peroxisome Proliferator-Activated Receptor Alpha Induce a Fiber-Type-Selective Transcriptional Response in Rat Skeletal Muscle Toxicol. Sci., August 1, 2006; 92(2): 578 - 586. [Abstract] [Full Text] [PDF]

				J. S. Lee, S. K. Pinnamaneni, S. J. Eo, I. H. Cho, J. H. Pyo, C. K. Kim, A. J. Sinclair, M. A. Febbraio, and M. J. Watt Saturated, but not n-6 polyunsaturated, fatty acids induce insulin resistance: role of intramuscular accumulation of lipid metabolites J Appl Physiol, May 1, 2006; 100(5): 1467 - 1474. [Abstract] [Full Text] [PDF]

				K. Yajima, H. Hirose, H. Fujita, Y. Seto, H. Fujita, K. Ukeda, K. Miyashita, T. Kawai, Y. Yamamoto, T. Ogawa, et al. Combination therapy with PPARgamma and PPARalpha agonists increases glucose-stimulated insulin secretion in db/db mice Am J Physiol Endocrinol Metab, May 1, 2003; 284(5): E966 - E971. [Abstract] [Full Text] [PDF]

				A. Chicco, M. E. D'Alessandro, L. Karabatas, C. Pastorale, J. C. Basabe, and Y. B. Lombardo Muscle Lipid Metabolism and Insulin Secretion Are Altered in Insulin-Resistant Rats Fed a High Sucrose Diet J. Nutr., January 1, 2003; 133(1): 127 - 133. [Abstract] [Full Text] [PDF]

				A. Andersson, C. Nalsen, S. Tengblad, and B. Vessby Fatty acid composition of skeletal muscle reflects dietary fat composition in humans Am. J. Clinical Nutrition, December 1, 2002; 76(6): 1222 - 1229. [Abstract] [Full Text] [PDF]

				Y. Nishimoto, T. Tomida, H. Matsui, T. Ito, and K. Okumura Decrease in Renal Medullary Endothelial Nitric Oxide Synthase of Fructose-Fed, Salt-Sensitive Hypertensive Rats Hypertension, August 1, 2002; 40(2): 190 - 194. [Abstract] [Full Text] [PDF]

				L. Madsen, M. Guerre-Millo, E. N. Flindt, K. Berge, K. J. Tronstad, E. Bergene, E. Sebokova, A. C. Rustan, J. Jensen, S. Mandrup, et al. Tetradecylthioacetic acid prevents high fat diet induced adiposity and insulin resistance J. Lipid Res., May 1, 2002; 43(5): 742 - 750. [Abstract] [Full Text] [PDF]

				D. M. Muoio, J. M. Way, C. J. Tanner, D. A. Winegar, S. A. Kliewer, J. A. Houmard, W. E. Kraus, and G. L. Dohm Peroxisome Proliferator-Activated Receptor-{alpha} Regulates Fatty Acid Utilization in Primary Human Skeletal Muscle Cells Diabetes, April 1, 2002; 51(4): 901 - 909. [Abstract] [Full Text] [PDF]

				D. A. Winegar, P. J. Brown, W. O. Wilkison, M. C. Lewis, R. J. Ott, W. Q. Tong, H. R. Brown, J. M. Lehmann, S. A. Kliewer, K. D. Plunket, et al. Effects of fenofibrate on lipid parameters in obese rhesus monkeys J. Lipid Res., October 1, 2001; 42(10): 1543 - 1551. [Abstract] [Full Text] [PDF]

				A. Cabrero, M. Alegret, R. M. Sanchez, T. Adzet, J. C. Laguna, and M. Vazquez Bezafibrate Reduces mRNA Levels of Adipocyte Markers and Increases Fatty Acid Oxidation in Primary Culture of Adipocytes Diabetes, August 1, 2001; 50(8): 1883 - 1890. [Abstract] [Full Text] [PDF]

				S. D. Clarke Polyunsaturated Fatty Acid Regulation of Gene Transcription: A Molecular Mechanism to Improve the Metabolic Syndrome J. Nutr., April 1, 2001; 131(4): 1129 - 1132. [Abstract] [Full Text]

				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]

				E. Montell, M. Turini, M. Marotta, M. Roberts, V. Noe, C. J. Ciudad, K. Mace, and A. M. Gomez-Foix DAG accumulation from saturated fatty acids desensitizes insulin stimulation of glucose uptake in muscle cells Am J Physiol Endocrinol Metab, February 1, 2001; 280(2): E229 - E237. [Abstract] [Full Text] [PDF]

				R. Buettner, C. B. Newgard, C. J. Rhodes, and R. M. O'Doherty Correction of diet-induced hyperglycemia, hyperinsulinemia, and skeletal muscle insulin resistance by moderate hyperleptinemia Am J Physiol Endocrinol Metab, March 1, 2000; 278(3): E563 - E569. [Abstract] [Full Text] [PDF]

				J. Berger, M. D. Leibowitz, T. W. Doebber, A. Elbrecht, B. Zhang, G. Zhou, C. Biswas, C. A. Cullinan, N. S. Hayes, Y. Li, et al. Novel Peroxisome Proliferator-activated Receptor (PPAR) gamma  and PPARdelta Ligands Produce Distinct Biological Effects J. Biol. Chem., March 5, 1999; 274(10): 6718 - 6725. [Abstract] [Full Text] [PDF]

				M. Guerre-Millo, P. Gervois, E. Raspe, L. Madsen, P. Poulain, B. Derudas, J.-M. Herbert, D. A. Winegar, T. M. Willson, J.-C. Fruchart, et al. Peroxisome Proliferator-activated Receptor alpha Activators Improve Insulin Sensitivity and Reduce Adiposity J. Biol. Chem., May 26, 2000; 275(22): 16638 - 16642. [Abstract] [Full Text] [PDF]

				Y. Nagai, Y. Nishio, T. Nakamura, H. Maegawa, R. Kikkawa, and A. Kashiwagi Amelioration of high fructose-induced metabolic derangements by activation of PPARalpha Am J Physiol Endocrinol Metab, May 1, 2002; 282(5): E1180 - E1190. [Abstract] [Full Text] [PDF]