Brain-derived neurotrophic factor (BDNF) and type 2 diabetes
Brain-derived neurotrophic factor (BDNF) and type 2 diabetes
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DOI：
10.1007/s00125-006-0537-4
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发表时间：
2007-02-01
期刊：
影响因子：
8.2
通讯作者：
Pedersen, B. K.
中科院分区：
文献类型：
--
作者：
Krabbe, K. S.;Nielsen, A. R.;Pedersen, B. K.
脑源性神经营养因子（BDNF）水平的降低与阿尔茨海默病和抑郁症的发病机制有关。这些疾病与2型糖尿病有关，动物模型表明BDNF在胰岛素抵抗中起作用。我们包括（研究1）233人，根据是否存在2型糖尿病和是否存在肥胖分为四组;和（研究2）7名健康志愿者，他们接受了高血糖和高胰岛素血症-在研究1中，在患有2型糖尿病的人中，BDNF的血浆水平降低，与肥胖无关。血浆BDNF与空腹血糖呈负相关，但与胰岛素无关。BDNF G196 A（Val 66 Met）多态性与糖尿病或肥胖之间没有关联。在研究2中，在基础条件下检测人脑BDNF的输出。当血糖水平升高时，这种输出被抑制。相反，当血浆胰岛素增加而血糖维持正常时，脑BDNF的输出不受抑制，这表明高水平的葡萄糖而不是胰岛素抑制人脑BDNF的输出，低水平的BDNF伴随着糖代谢受损。BDNF的减少可能是一个致病因素，不仅涉及痴呆和抑郁症，而且在2型糖尿病，可能解释了这些条件在流行病学研究中的集群。
Decreased levels of brain-derived neurotrophic factor (BDNF) have been implicated in the pathogenesis of Alzheimer's disease and depression. These disorders are associated with type 2 diabetes, and animal models suggest that BDNF plays a role in insulin resistance. We therefore explored whether BDNF plays a role in human glucose metabolism.We included (Study 1) 233 humans divided into four groups depending on presence or absence of type 2 diabetes and presence or absence of obesity; and (Study 2) seven healthy volunteers who underwent both a hyperglycaemic and a hyperinsulinaemic-euglycaemic clamp.Plasma levels of BDNF in Study 1 were decreased in humans with type 2 diabetes independently of obesity. Plasma BDNF was inversely associated with fasting plasma glucose, but not with insulin. No association was found between the BDNF G196A (Val66Met) polymorphism and diabetes or obesity. In Study 2 an output of BDNF from the human brain was detected at basal conditions. This output was inhibited when blood glucose levels were elevated. In contrast, when plasma insulin was increased while maintaining normal blood glucose, the cerebral output of BDNF was not inhibited, indicating that high levels of glucose, but not insulin, inhibit the output of BDNF from the human brain.Low levels of BDNF accompany impaired glucose metabolism. Decreased BDNF may be a pathogenetic factor involved not only in dementia and depression, but also in type 2 diabetes, potentially explaining the clustering of these conditions in epidemiological studies.