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

• Grant number: 18/12265-2
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: August 01, 2018
• End date: November 30, 2021
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Maria Lucia Cardillo Corrêa Giannella
• Grantee: Daniele Pereira dos Santos Bezerra
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 16/15603-0 - Unraveling mechanisms of glycemic control and chronic complications of Diabetes mellitus: contributions to human health, AP.TEM

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)

Scientific publications

(5)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

SANTOS-BEZERRA, DANIELE P.; CAVALEIRO, ANA MERCEDES; SANTOS, ARITANIA SOUSA; SUEMOTO, CLAUDIA KIMIE; PASQUALUCCI, CARLOS AUGUSTO; JACOB-FILHO, WILSON; PARAIZO LEITE, RENATA ELAINE; PASSARELLI, MARISA; NAGAHASHI MARIE, SUELY KAZUE; MACHADO, UBIRATAN FABRES; et al. Alcohol Use Disorder is Associated with Upregulation of MicroRNA-34a and MicroRNA-34c in Hippocampal Postmortem Tissue. ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH, v. 45, n. 1, p. 64-68, JAN 2021. (18/12265-2, 16/15603-0)

MOZÂNIA REIS DE MATOS; DANIELE PEREIRA SANTOS-BEZERRA; MARIA LUCIA CORREA-GIANNELLA. Reproducibility of a nylon fishing line as a screening test for diabetic foot ulceration risk. Clinics, v. 75, 2020-04-30. (18/12265-2)

MONTEIRO, MARIA BEATRIZ; SANTOS-BEZERRA, DANIELE P.; PELAES, TATIANA S.; VAIDYA, VISHAL S.; CORREA-GIANNELLA, MARIA LUCIA. MicroRNAs 1915-3p, 2861, and 4532 Are Associated with Long-Term Renal Function Decline in Type 1 Diabetes. CLINICAL CHEMISTRY, v. 65, n. 11, p. 1458-1459, NOV 2019. (16/04935-2, 16/15603-0, 15/19000-6, 18/12265-2)

DE MATOS, MOZANIA REIS; SANTOS-BEZERRA, DANIELE PEREIRA; DIAS CAVALCANTE, CRISTIANE DAS GRACAS; DE CARVALHO, JACIRA XAVIER; LEITE, JULIANA; JANUARIO NEVES, JOSE ANTONIO; ADMONI, SHARON NINA; PASSARELLI, MARISA; PARISI, MARIA CANDIDA; CORREA-GIANNELLA, MARIA LUCIA. Distal Symmetric and Cardiovascular Autonomic Neuropathies in Brazilian Individuals with Type 2 Diabetes Followed in a Primary Health Care Unit: A Cross-Sectional Study. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH, v. 17, n. 9, MAY 2020. (18/12265-2)

PEIXOTO, RENATA D'ALPINO; DONNARUMMA, CARLOS DEL CISTIA; MATHEUS, LUIZ HENRIQUE GOMES; SANTOS, ARITANIA SOUSA; SANTOS-BEZERRA, DANIELE PEREIRA; DE MATOS, MOZANIA REIS; NEVES, JOSE ANTONIO JANUARIO; CAMACHO, CLEBER PINTO; CORREA-GIANNELLA, MARIA LUCIA. Validation of Serum MicroRNAs-19a,-24, and-29a as Potential Markers to Differentiate Pancreatic Cancer-Associated Diabetes From Type 2 Diabetes Mellitus. PANCREAS, v. 51, n. 5, p. 2-pg., 2022-05-01. (18/20966-0, 18/12265-2)