Department of Medicine, Technische Universität Dresden, Dresden, Germany.
Department of Clinical Pathobiochemistry, Institute for Clinical Chemistry and Laboratory Medicine, Dresden, Germany.
Sci Rep. 2018 Jul 27;8(1):11335. doi: 10.1038/s41598-018-29434-2.
Diabetes mellitus is a group of disorders characterized by prolonged high levels of circulating blood glucose. Type 1 diabetes is caused by decreased insulin production in the pancreas whereas type 2 diabetes may develop due to obesity and lack of exercise; it begins with insulin resistance whereby cells fail to respond properly to insulin and it may also progress to decreased insulin levels. The brain is an important target for insulin, and there is great interest in understanding how diabetes affects the brain. In addition to the direct effects of insulin on the brain, diabetes may also impact the brain through modulation of the inflammatory system. Here we investigate how perturbation of circulating insulin levels affects the expression of Hes3, a transcription factor expressed in neural stem and progenitor cells that is involved in tissue regeneration. Our data show that streptozotocin-induced β-cell damage, high fat diet, as well as metformin, a common type 2 diabetes medication, regulate Hes3 levels in the brain. This work suggests that Hes3 is a valuable biomarker helping to monitor the state of endogenous neural stem and progenitor cells in the context of diabetes mellitus.
糖尿病是一组以循环血液中葡萄糖水平持续升高为特征的疾病。1 型糖尿病是由胰腺胰岛素产生减少引起的，而 2 型糖尿病可能由于肥胖和缺乏运动而发生；它始于胰岛素抵抗，即细胞对胰岛素不能正常反应，也可能进展为胰岛素水平降低。大脑是胰岛素的重要靶标，人们非常感兴趣的是了解糖尿病如何影响大脑。除了胰岛素对大脑的直接作用外，糖尿病还可能通过调节炎症系统来影响大脑。在这里，我们研究了循环胰岛素水平的波动如何影响 Hes3 的表达，Hes3 是一种在神经干细胞和祖细胞中表达的转录因子，参与组织再生。我们的数据表明，链脲佐菌素诱导的β细胞损伤、高脂肪饮食以及二甲双胍（一种常用的 2 型糖尿病药物）调节大脑中的 Hes3 水平。这项工作表明 Hes3 是一个有价值的生物标志物，有助于监测糖尿病背景下内源性神经干细胞和祖细胞的状态。
