{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T17:42:23Z","timestamp":1792690943353,"version":"4.5.0"},"reference-count":145,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2023,11,18]],"date-time":"2023-11-18T00:00:00Z","timestamp":1700265600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"FAPESP (Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo)","award":["#2016\/15603-0"],"award-info":[{"award-number":["#2016\/15603-0"]}]},{"name":"FAPESP (Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo)","award":["#2018\/26013-5"],"award-info":[{"award-number":["#2018\/26013-5"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The association of diabetes with cognitive dysfunction has at least 60 years of history, which started with the observation that children with type 1 diabetes mellitus (T1D), who had recurrent episodes of hypoglycemia and consequently low glucose supply to the brain, showed a deficit of cognitive capacity. Later, the growing incidence of type 2 diabetes mellitus (T2D) and dementia in aged populations revealed their high association, in which a reduced neuronal glucose supply has also been considered as a key mechanism, despite hyperglycemia. Here, we discuss the role of glucose in neuronal functioning\/preservation, and how peripheral blood glucose accesses the neuronal intracellular compartment, including the exquisite glucose flux across the blood\u2013brain barrier (BBB) and the complex network of glucose transporters, in dementia-related areas such as the hippocampus. In addition, insulin resistance-induced abnormalities in the hippocampus of obese\/T2D patients, such as inflammatory stress, oxidative stress, and mitochondrial stress, increased generation of advanced glycated end products and BBB dysfunction, as well as their association with dementia\/Alzheimer\u2019s disease, are addressed. Finally, we discuss how these abnormalities are accompained by the reduction in the expression and translocation of the high capacity insulin-sensitive glucose transporter GLUT4 in hippocampal neurons, which leads to neurocytoglycopenia and eventually to cognitive dysfunction. This knowledge should further encourage investigations into the beneficial effects of promising therapeutic approaches which could improve central insulin sensitivity and GLUT4 expression, to fight diabetes-related cognitive dysfunctions.<\/jats:p>","DOI":"10.3390\/ijms242216480","type":"journal-article","created":{"date-parts":[[2023,11,18]],"date-time":"2023-11-18T07:33:18Z","timestamp":1700292798000},"page":"16480","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["Glucose Transport and Utilization in the Hippocampus: From Neurophysiology to Diabetes-Related Development of Dementia"],"prefix":"10.3390","volume":"24","author":[{"given":"Caio Yogi","family":"Yonamine","sequence":"first","affiliation":[{"name":"Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Luiza Estimo","family":"Michalani","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo 05508-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafael Junges","family":"Moreira","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo 05508-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8237-2435","authenticated-orcid":false,"given":"Ubiratan Fabres","family":"Machado","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo 05508-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,11,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1161","DOI":"10.1016\/j.amjmed.2018.01.022","article-title":"Dementia","volume":"131","author":"Gale","year":"2018","journal-title":"Am. 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