Endocrinology, Department of Clinical and Experimental Medicine, University of Catania, Diabetes, Obesity and Dietetic Center, Garibaldi Hospital, Via Palermo n° 636, 95122 Catania, Italy.
Int J Mol Sci. 2018 Oct 24;19(11):3306. doi: 10.3390/ijms19113306.
In the last two decades, numerous in vitro studies demonstrated that insulin receptors and theirs downstream pathways are widely distributed throughout the brain. This evidence has proven that; at variance with previous believes; insulin/insulin-like-growth-factor (IGF) signalling plays a crucial role in the regulation of different central nervous system (CNS) tasks. The most important of these functions include: synaptic formation; neuronal plasticity; learning; memory; neuronal stem cell activation; neurite growth and repair. Therefore; dysfunction at different levels of insulin signalling and metabolism can contribute to the development of a number of brain disorders. Growing evidences demonstrate a close relationship between Type 2 Diabetes Mellitus (T2DM) and neurodegenerative disorders such as Alzheimer's disease. They, in fact, share many pathophysiological characteristics comprising impaired insulin sensitivity, amyloid β accumulation, tau hyper-phosphorylation, brain vasculopathy, inflammation and oxidative stress. In this article, we will review the clinical and experimental evidences linking insulin resistance, T2DM and neurodegeneration, with the objective to specifically focus on insulin signalling-related mechanisms. We will also evaluate the pharmacological strategies targeting T2DM as potential therapeutic tools in patients with cognitive impairment.
在过去的二十年中，大量的体外研究表明，胰岛素受体及其下游途径广泛分布于整个大脑。这一证据证明，与之前的观点不同，胰岛素/胰岛素样生长因子（IGF）信号在调节不同的中枢神经系统（CNS）功能中起着至关重要的作用。其中最重要的功能包括：突触形成；神经元可塑性；学习；记忆；神经元干细胞激活；神经突生长和修复。因此，胰岛素信号和代谢的不同水平的功能障碍可能导致许多脑部疾病的发生。越来越多的证据表明，2 型糖尿病（T2DM）与神经退行性疾病（如阿尔茨海默病）之间存在密切关系。它们实际上有许多共同的病理生理特征，包括胰岛素敏感性受损、β-淀粉样蛋白积累、tau 过度磷酸化、脑血管病变、炎症和氧化应激。在本文中，我们将回顾与胰岛素抵抗、T2DM 和神经退行性变相关的临床和实验证据，目的是特别关注与胰岛素信号相关的机制。我们还将评估针对 T2DM 的药物治疗策略作为认知障碍患者的潜在治疗工具。
