Programa Multicêntrico de Pós-Graduação em Ciências Fisiológicas- Sociedade Brasileira de Fisiologia (SBFis), Universidade Federal dos Vales do Jequitinhonha E Mucuri (UFVJM), Campus JK, Rodovia MGT 367, Km 583, Alto da Jacuba, no 5000, Diamantina, MG, CEP 39100-000, Brazil.
Faculty of Medicine and Health, Sydney School of Health Sciences, The University of Sydney, Sydney, Australia.
Mol Biol Rep. 2020 Aug;47(8):6347-6356. doi: 10.1007/s11033-020-05693-z. Epub 2020 Aug 1.
Alzheimer's disease (AD) and type 2 diabetes (T2D) major feature is insulin resistance. Brain and peripheral insulin resistance lead to hyperglycemia, which contributes to the development of T2D-linked comorbidities, such as obesity and dyslipidemia. Individuals with hyperglycemia in AD present with neuronal loss, formation of plaques and tangles and reduced neurogenesis. Inflammation seems to play an essential role in the development of insulin resistance in AD and T2D. We conducted a literature review about the links between AD and T2D. Alterations in glucose metabolism result from changes in the expression of the insulin receptor substrates 1 and 2 (IRS-1 and IRS-2), and seem to be mediated by several inflammatory pathways being present in both pathologies. Although there are some similarities in the insulin resistance of AD and T2D, brain and peripheral insulin resistance also have their discrete features. Failure to activate IRS-1 is the hallmark of AD, while inhibition of IRS-2 is the main feature in T2D. Inflammation mediates the alterations in glucose metabolism in AD and T2D. Targeting inflammation and insulin receptors may be a successful strategy to prevent and ameliorate T2D and AD symptoms.
阿尔茨海默病(AD)和 2 型糖尿病(T2D)的主要特征是胰岛素抵抗。脑和外周胰岛素抵抗导致高血糖,这有助于发展与 T2D 相关的合并症,如肥胖和血脂异常。AD 中伴有高血糖的个体表现出神经元丧失、斑块和缠结形成以及神经发生减少。炎症似乎在 AD 和 T2D 中胰岛素抵抗的发展中起着至关重要的作用。我们对 AD 和 T2D 之间的联系进行了文献回顾。葡萄糖代谢的改变是由于胰岛素受体底物 1 和 2(IRS-1 和 IRS-2)的表达变化引起的,并且似乎由两种病理中存在的几种炎症途径介导。尽管 AD 和 T2D 的胰岛素抵抗存在一些相似之处,但脑和外周胰岛素抵抗也有其独特的特征。IRS-1 激活失败是 AD 的标志,而 IRS-2 抑制是 T2D 的主要特征。炎症介导 AD 和 T2D 中葡萄糖代谢的改变。靶向炎症和胰岛素受体可能是预防和改善 T2D 和 AD 症状的成功策略。