Brain insulin resistance in type 2 diabetes and Alzheimer disease: concepts and conundrums.
Brain insulin resistance in type 2 diabetes and Alzheimer disease: concepts and conundrums.
复制标题
DOI：
10.1038/nrneurol.2017.185
复制
发表时间：
2018-03
期刊：
影响因子：
--
通讯作者：
Nathan DM
中科院分区：
文献类型：
--
作者：
Arnold SE;Arvanitakis Z;Macauley-Rambach SL;Koenig AM;Wang HY;Ahima RS;Craft S;Gandy S;Buettner C;Stoeckel LE;Holtzman DM;Nathan DM
阿尔茨海默病和相关痴呆（ADRD）和2型糖尿病（T2DM）是我们这个时代最紧迫的两种流行病，其风险因素、合并症和假定的病理生理学机制存在相当大的重叠。关于每种疾病的生物学已知很多，但T2DM和ADRDs是否是由衰老的巧合根源引起的平行现象，还是由恶性病理生理循环联系起来的协同疾病，仍不清楚。胰岛素抵抗是T2DM的一个核心特征，并且正在成为ADRD的一个潜在重要特征。在此，我们回顾了关于胰岛素在大脑中信号传导的关键观察和实验数据，重点介绍了胰岛素在神经元和胶质细胞中的作用。此外，我们定义了“脑胰岛素抵抗”的概念，并回顾了越来越多的关于2型糖尿病、肥胖和胰岛素抵抗中认知障碍和神经病理学异常的文献，尽管这些文献仍然不一致。最后，我们回顾了ADRD中内源性脑胰岛素抵抗的证据。通过扩展我们对这些疾病的重叠机制的理解，我们希望加速2型糖尿病和ADRDs认知功能障碍的预防性、疾病改善和对症治疗的合理开发。
Considerable overlap has been identified in the risk factors, comorbidities and putative pathophysiological mechanisms of Alzheimer disease and related dementias (ADRDs) and type 2 diabetes mellitus (T2DM), two of the most pressing epidemics of our time. Much is known about the biology of each condition, but whether T2DM and ADRDs are parallel phenomena arising from coincidental roots in ageing or synergistic diseases linked by vicious pathophysiological cycles remains unclear. Insulin resistance is a core feature of T2DM and is emerging as a potentially important feature of ADRDs. Here, we review key observations and experimental data on insulin signalling in the brain, highlighting its actions in neurons and glia. In addition, we define the concept of ‘brain insulin resistance’ and review the growing, although still inconsistent, literature concerning cognitive impairment and neuropathological abnormalities in T2DM, obesity and insulin resistance. Lastly, we review evidence of intrinsic brain insulin resistance in ADRDs. By expanding our understanding of the overlapping mechanisms of these conditions, we hope to accelerate the rational development of preventive, disease-modifying and symptomatic treatments for cognitive dysfunction in T2DM and ADRDs alike.
登录
查看更多内容
影响因子：
4.3
作者：
Berhane, Feven;Fite, Alemu;Seyoum, Berhane
通讯作者：
Seyoum, Berhane
影响因子：
3.7
作者：
Benedict, C;Hallschmid, M;Kern, W
通讯作者：
Kern, W
影响因子：
5.3
作者：
Abbott, MA;Wells, DG;Fallon, JR
通讯作者：
Fallon, JR
影响因子：
9.9
作者：
Beeri, M. S.;Schmeidler, J.;Haroutunian, V.
通讯作者：
Haroutunian, V.
影响因子：
5
作者：
Banks, WA
通讯作者：
Banks, WA