Alterations in glucose metabolism on cognition: A possible link between diabetes and dementia

Rodrigo E. González-Reyes, Gjumrakch Aliev, Marco Ávila-Rodrigues, George E. Barreto

Research output: Contribution to journalArticlepeer-review

68 Scopus citations


The use of the carbohydrate glucose as an energetic source is essential for an adequate function of the human body. The complex regulation of this molecule involves the coordinated action of various organs such as pancreas, liver and brain. Any disruption of this physiological balance may result in a dangerous compromise of general metabolic activities increasing the possibility of developing T1DM, T2DM and possibly AD. Astrocytes convert glucose into lactate and transfer it to neurons. This lactate is essential for neuronal metabolism and for various processes including the formation of synapses, dendrites and the expression of genes involved in memory. The brain is highly susceptible to variations in glucose blood levels, and both hypoglycemia and hyperglycemia can be dangerous. Pathological hyperglycemia induces changes in plasmatic osmotic pressure, mitochondrial production of free radicals, oxidative stress and activation of neuronal apoptosis, among others. Both AD and diabetes are chronic diseases having age as an important risk factor. As the brain ages, it seems to become much more susceptible to cellular damage induced by excess of circulating glucose and this could explain the appearance of cognitive changes observed in some patients with diabetes. Excessive circulation of pro-inflammatory agents has been observed in insulin resistance and is likely that some of these mediators may cross the bloodbrain barrier and induce abnormal neuroinflammation. GSK-3 is overexpressed in diabetes and also has been reported to regulate tau phosphorylation and production of A peptides in the brain. Currently, diabetes (hyperglycemia) is considered as a risk factor for the de- velopment of AD. A novel therapeutic approach, using intranasal insulin and anti-diabetic medications in patients suffering from AD is being explored and is discussed in this review.

Original languageEnglish (US)
Pages (from-to)812-818
Number of pages7
JournalCurrent Pharmaceutical Design
Issue number7
StatePublished - Feb 1 2016
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Drug Discovery


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