Insulin-dependent Diabetes Mellitus in Mice Does Not Alter Liver Heparan Sulfate
Insulin-dependent Diabetes Mellitus in Mice Does Not Alter Liver Heparan Sulfate
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DOI：
10.1074/jbc.m110.112391
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发表时间：
2010-05-07
影响因子：
4.8
通讯作者：
Esko, Jeffrey D.
中科院分区：
文献类型：
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作者：
Bishop, Joseph R.;Foley, Erin;Esko, Jeffrey D.
糖尿病相关的高脂血症通常归因于血浆脂蛋白，特别是富含胆固醇和甘油三酯的残余脂蛋白的清除减少。肝清除残余物通过低密度脂蛋白受体和硫酸乙酰肝素蛋白聚糖，syndecan-1。先前的研究表明，在大鼠和小鼠糖尿病模型中硫酸乙酰肝素蛋白聚糖代谢的改变，与糖尿病血脂异常可能是由肝脏中蛋白聚糖表达的改变引起的观点一致。在这项研究中，我们分析了链脲佐菌素诱导的胰岛素缺乏型糖尿病小鼠肝脏硫酸乙酰肝素的含量和组成，这些小鼠显示空腹高血糖症和饮食中富含乙酰肝素的脂蛋白的清除延迟。正常和糖尿病同窝仔之间没有差异，肝硫酸乙酰肝素含量，硫酸化，syndecan-1蛋白水平，或肝素结合配体的亲和力，如载脂蛋白E或成纤维细胞生长因子-2，注意到。在体内胰岛素缺乏小鼠中观察到[S-35]硫酸盐掺入减少，但该减少是由于血浆无机硫酸盐增加，这降低了肝脏硫酸乙酰肝素的标记效率。这些结果表明，胰岛素缺乏小鼠的高脂血症不是由于肝脏硫酸乙酰肝素组成的变化。
Diabetes-associated hyperlipidemia is generally attributed to reduced clearance of plasma lipoproteins, especially remnant lipoproteins enriched in cholesterol and triglycerides. Hepatic clearance of remnants occurs via low density lipoprotein receptors and the heparan sulfate proteoglycan, syndecan-1. Previous studies have suggested alterations in heparan sulfate proteoglycan metabolism in rat and mouse diabetic models, consistent with the idea that diabetic dyslipidemia might be caused by alterations in proteoglycan expression in the liver. In this study we analyzed the content and composition of liver heparan sulfate in streptozotocin-induced insulin-deficient diabetic mice that displayed fasting hypertriglyceridemia and delayed clearance of dietary triglyceride-rich lipoproteins. No differences between normal and diabetic littermates in liver heparan sulfate content, sulfation, syndecan-1 protein levels, or affinity for heparin-binding ligands, such as apolipoprotein E or fibroblast growth factor-2, were noted. Decreased incorporation of [S-35] sulfate in insulin-deficient mice in vivo was observed, but the decrease was due to increased plasma inorganic sulfate, which reduced the efficiency of labeling of liver heparan sulfate. These results show that hyperlipidemia in insulin-deficient mice is not due to changes in hepatic heparan sulfate composition.