Elucidation of etiology in diabetic dyslipidemia and VLDL receptor expression

高脂血症是糖尿病的常见特征，与心血管疾病密切相关。极低密度脂蛋白受体（VLDL-R）是低密度脂蛋白受体（LDL-R）家族的成员，它能高度特异性地结合并内化富含甘油三酯（TG）的脂蛋白。我们研究了胰岛素缺乏状态下高脂血症的病因。用链脲佐菌素（STZ）诱导大鼠心肌和骨骼肌VLDL-R的表达，并观察了VLDL-R在高脂血症大鼠心肌和骨骼肌中的表达。诱发糖尿病。STZ大鼠表现出严重的高脂血症，骨骼肌（&gt;90%）、心脏（&gt;90%）和心肌（&gt;90%）中的VLDL-R蛋白显著下降。（约50%）和脂肪组织本身的损失。骨骼肌中VLDL-R蛋白的减少不能用转录水平的减少来解释，VLDL-R mRNA仅降低约25%，肝脏中LDL受体和LDL受体相关蛋白（LRP-1）的表达没有一致的变化。在STZ大鼠中，观察到对肝脏中VLDL-TG的产生没有影响，而肝素后血浆脂蛋白脂酶（LPL）活性降低。在大鼠肌管细胞中，胰岛素（10 μ <-6>M）或IGF-1（10 ng/ml）恢复了降低的VLDL受体蛋白。这些结果表明，VLDL-R缺乏和血浆LPL活性降低有助于胰岛素缺乏型糖尿病的高脂血症。

Hyperlipidemia is a common feature of diabetes and is related to cardiovascular disease.The very low-density lipoprotein receptor(VLDL-R) is a member of the low-density lipoprotein receptor(LDL-R) family.It binds and internalizes triglyceride(TG)-rich lipoproteins with high specificity.We examined the etiology of hyperlipidemia in insulin deficient state.VLDL-R expression in heart and skeletal muscle were measured in rats with streptozotocin(STZ)-induced diabetes. STZ rats showed severe hyperlipidemia with a dramatic decline in VLDL-R protein in skeletal muscle (>90%), heart(about 50%) and a loss of adipose tissues itself on day 28.The reduction of VLDL-R protein in skeletal muscle could not be explained by a decrease at transcriptional level, as VLDL-R mRNA was reduced by only about 25%.The expression of the LDL receptor and LDL receptor-related protein(LRP-1) in liver showed no consistent changes.Furthermore, no effect on VLDL-TG production in liver was observed in STZ rats, whereas post-heparin plasma lipoprotein lipase(LPL)activity was reduced.In rat myotuble cells, insulin (10^<-6>M) or IGF-1 (10 ng/ml)recovered the decreased VLDL receptor proteins. These results suggest that both VLDL-R deficiency and reduced plasma LPL activity contribute to hyperlipidemia in insulin-deficient diabetes.