Title:Alterations in Glucose Metabolism on Cognition: A Possible Link Between Diabetes and Dementia
Volume: 22
Issue: 7
Author(s): Rodrigo E. González-Reyes, Gjumrakch Aliev, Marco Avila-Rodrigues and George E. Barreto
Affiliation:
Keywords:
Diabetes, Alzheimer Disease, dementia, insulin resistance, antidiabetic drugs.
Abstract: 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 Aβ peptides in the brain. Currently, diabetes (hyperglycemia) is considered as a risk factor for the development
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.