4.5 Review

An update on potential links between type 2 diabetes mellitus and Alzheimer's disease

Journal

MOLECULAR BIOLOGY REPORTS
Volume 47, Issue 8, Pages 6347-6356

Publisher

SPRINGER
DOI: 10.1007/s11033-020-05693-z

Keywords

Insulin resistance; Inflammation; Cognitive impairment; Memory loss; Disease

Funding

  1. Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior-Brasil (CAPES) [001]

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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.

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