Changes in the glucose transporters expression in central nervous system: correlation between Type 3 Diabetes mellitus and Alzheimer's Disease

Abstract

Epidemiological studies have shown that Diabetes mellitus and Obesity are risk factors for the genesis and progression of Alzheimer's Disease. In the last decade, studies have demonstrated insulin resistance in some brain regions of patients with Alzheimer's Disease (AD), suggesting that impairment of glucose supply to neuronal cells may be a key element in the onset and progression of neurodegeneration in AD. In regions that are frequently involved in AD, such as the hippocampus, caudate nucleus and cerebellum, expression of GLUT4 and SGLT1 glucose transporters, encoded by the SLC2A4 and SLC5A1 genes, respectively, has been suggested. Expression of the glucose transporters have already been shown to be altered in peripheral tissues of individuals with insulin resistance and/or Diabetes. GLUT2, encoded by the SLC2A2 gene, is expressed in regions devoid of blood-brain barrier, such as the hypothalamus, and has also been related to the pathogenesis of AD. Also, recent studies suggest that epigenetic mechanisms can regulate the transcription of important genes in the pathophysiology of AD; we have already shown epigenetic changes in the SLC2A4 gene in muscle of diabetic rats, but nothing is known about this in the brain. Thus, the focus of the present project is to investigate, in areas of (post-mortem) brains of obese humans whether Diabetes alters the expression of SLC2A4/GLUT4, SLC2A2/GLUT2, SLC5A1/SGLT1, and of inflammatory markers. (AU)