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Diabetes and insulin in regulation of brain cholesterol metabolism.

机译:糖尿病和胰岛素调节脑胆固醇代谢。

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The brain is the most cholesterol-rich organ in the body, most of which comes from in situ synthesis. Here we demonstrate that in insulin-deficient diabetic mice, there is a reduction in expression of the major transcriptional regulator of cholesterol metabolism, SREBP-2, and its downstream genes in the hypothalamus and other areas of the brain, leading to a reduction in brain cholesterol synthesis and synaptosomal cholesterol content. These changes are due, at least in part, to direct effects of insulin to regulate these genes in neurons and glial cells and can be corrected by intracerebroventricular injections of insulin. Knockdown of SREBP-2 in cultured neurons causes a decrease in markers of synapse formation and reduction of SREBP-2 in the hypothalamus of mice using shRNA results in increased feeding and weight gain. Thus, insulin and diabetes can alter brain cholesterol metabolism, and this may play an important role in the neurologic and metabolic dysfunction observed in diabetes and other disease states.
机译:大脑是人体中胆固醇含量最高的器官,其中大部分来自原位合成。在这里,我们证明,在胰岛素缺乏型糖尿病小鼠中,胆固醇代谢的主要转录调节因子SREBP-2及其下游基因在下丘脑和其他大脑区域的表达减少,从而导致大脑减少胆固醇的合成和突触体胆固醇的含量。这些变化至少部分是由于胰岛素在神经元和神经胶质细胞中调节这些基因的直接作用所致,并且可以通过脑室内注射胰岛素来纠正。使用shRNA敲低培养的神经元中的SREBP-2会导致突触形成标记的减少以及下丘脑中SREBP-2的减少,从而导致进食和体重增加。因此,胰岛素和糖尿病可以改变脑胆固醇代谢,这可能在糖尿病和其他疾病状态下观察到的神经和代谢功能异常中起重要作用。

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