Changes in the flux of hexosamine biosynthesis pathway in skeletal muscle of rats with insusulin resistance induced by high fat diet

Abstract

Objective To investigate the effect of hexosamine biosynthesis pathway on the development of insulin resistance induced by high fat diet. Methods Normal male SD rats were randomly divided into three groups： control（fed with normal chow）, high fat （fed with high fat diet for 13 weeks）, and rosiglitazone （intragastric administration with rosiglitazone for 5 weeks ）groups. After 13 weeks, all the rats were sacrificed, serum and muscle triglycerides（ TG）, serum total cholesterol （TC）, and serum and muscle free fatty acids （FFA） were measured. Insulin sensitivity was evaluated by insulin sensitivity index （ISI）and glucose infused rat（GIR） with the hyperinsulinemic euglycemic clamp technique. The flux of HBP in skeletal muscle was detected with the expression level of glutamine-fiuctose-6-phosphate transaminase （GFAT） mRNA （ RT-PCR）, the content of UDP- GlcNAc （HPLC） and the level of O-GlcNAc glycosylation in skeletal muscle proteins （Western blot ）. Results Compared with control group, serum TG, TC, FFA and muscle TG, FFA levels of high fat group increased（ all P〈0.01 ）, both ISI and GIR decreased（ both P〈0.01 ）, and the levels of GFAT mRNA （0.51 ± 0.05 vs 0. 18± 0.02）, UDP-GlcNAc[ （6.18±0.86 vs 2.42±0.36） nmol/g], and O-GlcNAc glycosylation of skeletal muscle proteins in high fat group were raised （ all P〈0. 01 ）. In rosiglitazone group, serum and muscle TG, FFA were deceased（ all P〈0. 01 ）, insulin sensitivity was increased （ P〈0. 05 ） and the flux of HBP[ GFAT mRNA 0. 27±0. 03 , UDP-GlcNAc（2.62±0.32）nmol/g] was reduced （all P〈0.05） as compared with high fat group. Conclusions High fat diet-induced insulin resistance in rats is correlated with the increased flux of HBP in skeletal muscle, which is decreased by rosiglitazone. Key words: Hexosamine biosynthesis pathway; Insulin resistance; High fat diet ; Rosiglitazone