摘要目的 探讨已糖胺通路(HBP)在高脂饲料诱导胰岛素抵抗形成中的作用.方法 雄性SD大鼠随机分为3组:对照组、高脂组和罗格列酮组.13周后,检测大鼠血清甘油三酯(TG)、总胆固醇(TC)、游离脂肪酸(FFA)、骨骼肌中TG和FFA的含量,胰岛素敏感性采用胰岛素敏感指数(ISI)和高胰岛素正糖钳夹试验稳态时的葡萄糖输注率(GIR)来评估,骨骼肌HBP的流量用谷氨酰胺:6-磷酸果糖转氨酶(GFAT)mRNA的表达水平、二磷酸尿嘧啶-N-乙酰葡萄糖胺(UDP-GlcNAc)的含量及蛋白O-GIcNAc糖基化水平来衡量.结果 高脂组大鼠与对照组相比,血清TG、TC、FFA以及骨骼肌TG、FFA均升高(均P<0.01);ISI、GIR均降低(均P<0.01),骨骼肌GFAT mRNA的表达(0.51±0.05对0.18±0.02)、UDP-GlcNAc 含量[(6.18±0.86对2.42±0.36)nmol/g]以及蛋白O-GlcNAc糖基化水平均明显升高(均P<0.01).罗格列酮组大鼠与高脂组相比,血清和骨骼肌TG、FFA明显降低(均P<0.01),胰岛素敏感性提高(P<0.05),GFAT mRNA的表达(0.27±0.03)、UDP-GlcNAc含量[(2.62±0.32)nmol/g]以及蛋白O-GIeNAc糖基化水平均明显降低(均P<0.05).结论 高脂饲料诱导大鼠胰岛素抵抗与其增加骨骼肌HBP的流量相关,可被罗格列酮降低.

abstractsObjective 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 wss evaluated by insulin sensitivity index(ISI)and glucose infused rat(GIR) with the hyperinsulinemic englycemic clamp technique.The flux of HBP in skeletal muscle was detected with the expression level of glutamine-fructose-6-phosphate transaminase(GFAT)mRNA(RT-PCR),the content of UDPGlcNAc(HPLC)and the level of O-GlcNAc glycosylation in skeletal muscle proteins(Western blot). Results Compared with control group,senlm TG,TC,FFA and muscle TG,FFA levels of high fat group increased(aII P<0.01).both ISI and GIR decreased(both P<0.01),and the leveIs 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-GIcNAc glycosylation of skeletal muscle proteins in high fat group were raised(all P<0.01).In rosiglitazone group,serum and muscle TG.FFA welc deceased(all P<0.01).insulin sensitivity was increased(P<0.05)and the flux of HBP[GFAT mRNA 0.27±0.03,UDP-GIcNAc(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 skeletaI muscle.which is decreased by rosiglitazone.