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

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Abstract

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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Fig. 1

Adapted from Sousa [26]

Fig. 2
Fig. 3

Adapted from De Felice; Ferreira [116]

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Acknowledgements

We are thankful to Coordenação de Pessoal de Ensino Superior (CAPES) and Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG). We also thank to the CIPq-Saúde of UFVJM for the physical support to the development of this study.

Funding

This study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior—Brasil (CAPES)—Finance Code 001.

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Authors and Affiliations

  1. 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

    Ricardo Augusto Leoni De Sousa, Daniel Almeida Freitas, Vanessa Amaral Mendonça, Ana Cristina Rodrigues Lacerda & Hércules Ribeiro Leite

  2. Faculty of Medicine and Health, Sydney School of Health Sciences, The University of Sydney, Sydney, Australia

    Alison R. Harmer

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  1. Ricardo Augusto Leoni De Sousa
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  2. Alison R. Harmer
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  3. Daniel Almeida Freitas
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  4. Vanessa Amaral Mendonça
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  6. Hércules Ribeiro Leite
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Contributions

RALS conceived the review and performed the literature search; RALS wrote the manuscript, with contributions from ARH; RALS, ARH, DAF, VAM, ACRL, HRL analyzed and critically discussed the data and reviewed the manuscript; RALS and HRL supervised the review. All authors have read and approved the final version of the manuscript, and agree with the order of presentation of the authors.

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Correspondence to Ricardo Augusto Leoni De Sousa.

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De Sousa, R.A.L., Harmer, A.R., Freitas, D.A. et al. An update on potential links between type 2 diabetes mellitus and Alzheimer’s disease. Mol Biol Rep 47, 6347–6356 (2020). https://doi.org/10.1007/s11033-020-05693-z

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