Mice lacking phosphatidylinositol transfer protein-α exhibit spinocerebellar degeneration, intestinal and hepatic steatosis, and hypoglycemia
Mice lacking phosphatidylinositol transfer protein-α exhibit spinocerebellar degeneration, intestinal and hepatic steatosis, and hypoglycemia
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DOI：
10.1074/jbc.m303591200
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发表时间：
2003-08-29
影响因子：
4.8
通讯作者：
Bankaitis, VA
中科院分区：
文献类型：
--
作者：
Alb, JG;Cortese, JD;Bankaitis, VA
磷脂酰肌醇转移蛋白（PITP）调节脂质代谢和细胞功能之间的界面。我们现在报告，消融PITPalpha功能导致aponecrotic脊髓小脑疾病，低血糖症，肠道和肝脏脂肪变性的小鼠。数据表明，低血糖症部分与胰高血糖素原基因表达减少和胰岛细胞缺陷导致的糖原分解有关。肠和肝脂肪变性是由于中性脂质和游离脂肪酸物质在这些器官中的细胞内积聚所致，表明甘油三酯和二酰基甘油从内质网的运输缺陷。我们认为肠道和肝脏脂质代谢紊乱和胰高血糖素原基因表达缺陷导致PITPalpha（-/-）小鼠低血糖，低血糖是脊髓小脑疾病发病的重要因素。总之，这些数据表明PITPalpha在葡萄糖稳态和哺乳动物内质网功能中具有意想不到的作用，这些功能与特定管腔脂质货物的运输相关联。
Phosphatidylinositol transfer proteins (PITPs) regulate the interface between lipid metabolism and cellular functions. We now report that ablation of PITPalpha function leads to aponecrotic spinocerebellar disease, hypoglycemia, and intestinal and hepatic steatosis in mice. The data indicate that hypoglycemia is in part associated with reduced proglucagon gene expression and glycogenolysis that result from pancreatic islet cell defects. The intestinal and hepatic steatosis results from the intracellular accumulation of neutral lipid and free fatty acid mass in these organs and suggests defective trafficking of triglycerides and diacylglycerols from the endoplasmic reticulum. We propose that deranged intestinal and hepatic lipid metabolism and defective proglucagon gene expression contribute to hypoglycemia in PITPalpha(-/-) mice, and that hypoglycemia is a significant contributing factor in the onset of spinocerebellar disease. Taken together, the data suggest an unanticipated role for PITPalpha in with glucose homeostasis and in mammalian endoplasmic reticulum functions that interface with transport of specific luminal lipid cargoes.