Lipids and insulin resistance in an experimental model of dyslipidemia. Rats fed chronically a sucrose-rich diet develop hypertriglyceridemia, moderate hyperglycemia, insulin resistance and adiposity. The goal of this work was to study in this animal model some metabolic pathways that might account for the lipid accumulation in the skeletal muscle and it relationship with dyslipidemia, altered insulin secretion from perifused islets and whole body insulin resistance. For this purpose male Wistar rats initially weighting 180-190 g were fed during 30 weeks with a purified sucrose-rich diet (SRD) containing by weight (g/100g ): 63 sucrose, 17 casein free vitamins, 5 corn oil, 10 cellulose, 3.5 salt mixture (AIN-93MX), 1 vitamin mixture (AIN-93-VX), 0.2 choline and 0.3 DL- ethionine. The control group received the same purified diet, but sucrose replaced by corn-starch [high starch diet (CD)]. The rats had free access to food and water and consumed their respective diets for up to 30 weeks. Both diets were isoenergetic and provided approximately 15.28 kJ/g of food. Rats were fed “ad- libitum” during the complete experimental period. The following results were obtained: A) The biphasic patterns of glucose-stimulated insulin secretion from perifused islets showed an absence of the first peak with an increase of the second phase of hormone secretion. Moreover, compared to rats fed a control diet (CD) a significant reduction of the glucose infusion rate (GIR) was observed. Values were as follows: GIR (mg/kg.min.), mean ± SEM (n= 6), 4.3±0.80 in SRD vs 10±1.1 in CD (p<0.05). B) A significant increase (p<0.05) of both triglyceride and long-chain acyl -CoA contents in the gastrocnemius muscle was accompanied by an impaired capacity of glucose oxidation in the basal state and uring the euglycemic –hyperinsulinemic clamp studies. This was mainly due to a decrease (p<0.05) of the active form of the pyruvate dehydrogenase complex (PDHa) and an increase of the PDH-Kinase activities (p<0.05). A significant reduction of the flux through the PDH complex may limit glucose oxidation via glucose-fatty acid cycle of Randle. Besides, an impaired non-oxidative pathway of glucose was recorded at the end of the clamp. The glycogen synthase activity was significantly lower (p<0.05) as compared with age matched control rats fed a CD. Furthermore, a decreased insulin-stimulated glycogen store was observed. C) A high level of both long-chain acyl -CoA and diacylglycerol within the skeletal muscle could stimulate an increase and translocation of nPKCq isozyme to the cell membrane and this could interfere with insulin signaling pathways. Our data suggest that in the gastrocnemius muscle of rats fed a SRD over an extended period of time increased availability and oxidation of lipid fuel contributed to the abnormal insulin sensitivity and the whole body insulin resistance. Literature cited: Cheal, K.L.; Abbasi, F.; Lamendola, E. et al. Relationship to insulin resistance of the adult treatment panel III diagnostic criteria for identification of the metabolic syndrome. Diabetes 53: 1195-1200, 2004. Stannard, S.R.; Johson N.A. Insulin resistance and elevated triglycerides in muscle: more important for survival than “thirty” genes? J Physiol 3: 595-607, 2003. Yu, C.; Chen, Y.; Cline, G.W. et al. Mechanism by which fatty acid inhibits insulin activation of insulin receptor substrate-1 (IRS-1) associated phosphatidyl inositol-3-kinase activity in muscle. J Biol Chem 277: 50230-50236, 2002. Rossi, A.; Lombardo, Y.B.; Lacorte, J.M. et al. Dietary fish oil positively regulates plasma leptin and adiponectin levels in sucrose-fed insulin-resistant rats. Am J Physiology 289: R486-R494, 2005. Chicco, A.; Basabe, J.C.; Karabatas, L. et al. Troglytazone (CS-045) normalizes hypertriglyceridemia and restores the altered patterns of glucose-stimulated insulin secretion in dyslipemic rats. Metabolism 49: 1346-1351, 2000. Lewis, G.F.; Carpentier, A.; Adeli, K. et al. Disorder fat storage and mobilization in the pathogenesis of insulin resistance and type 2 Diabetes. Endocr