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Integrative proteomic and microRNA analysis of the intestine of mice with Type 2 Diabetes Mellitus treated with different concentrations of fluoride in drinking water

Grant number: 19/26117-8
Support Opportunities:Scholarships in Brazil - Post-Doctoral
Effective date (Start): July 01, 2020
Effective date (End): October 31, 2023
Field of knowledge:Health Sciences - Dentistry - Social and Preventive Dentistry
Principal Investigator:Marília Afonso Rabelo Buzalaf
Grantee:Aline Dionizio Valle
Host Institution: Faculdade de Odontologia de Bauru (FOB). Universidade de São Paulo (USP). Bauru , SP, Brazil


Diabetes Mellitus (DM) is considered a disease of great impact and the prospects are that it should increase considerably in the coming years, due to people's lifestyles. Among the two types of diabetes mellitus, type 2 (DM2) is the most prevalent (90%). The pathogenesis of DM2 is very complex and is involved with a progression of insulin resistance in the liver and peripheral tissues, which is further accompanied by a defective insulin secretion by pancreatic ² cells, leading to an abnormal increase in blood glucose. Some studies have indicated that fluoride (F) may influence insulin resistance/sensitivity, an early feature of DM2 development. Thus, studies relating this pathology to the administration of F are important, since this ion is present in water supply and other sources, such as toothpaste and food. As the main route of F absorption is the Gastrointestinal Tract (GIT) and the main organ is the intestine, the aim of this study is to evaluate the proteomic and miRNA changes caused by F in the intestine of animals with DM2, induced by hyperlipidic diet and streptozotocin administration, besides implementing a new line of research (miRNA analysis) in the biochemistry laboratory of the Bauru School of Dentistry - USP. Eighteen mice adult male (C57BL/6J) will be used and divided into 3 experimental groups (n = 6) according to the dose of F (0, 10 or 50 mgF/L) administered by drink. The animals will receive a hyperlipidic diet and after reaching 30g and at least 8 weeks, will receive daily intraperitoneal streptozotocin (STZ) injections of 40mg/kg for 3 to 5 days. From the 4th week will begin treatment with F, lasting 21 days. Blood glucose will be measured weekly using a glycemic monitor (Accu-Check Performa, Roche Diagnostics, Mannheim, Germany) to detect insulin resistance, and after STZ administration and DM2 testing. A group of 6 mice (C57BL /6) will be used as control. They will receive for the same experimental period, water without F and normocaloric diet. After the experimental period, the animals will be euthanized for sample collection, and blood will be collected for F analysis (specific ion electrode), as well as the intestine for marker-free quantitative proteomic analysis (Protein Linx Global Service software) and microRNA. After verifying the normality and homoscedasticity of the data, they will be submitted to the appropriate statistical analysis (p <0.05). (AU)

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Scientific publications
(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)
MIOTTO, DANYELLE SIQUEIRA; DUCHATSCH, FRANCINE; DIONIZIO, ALINE; BUZALAF, MARILIA AFONSO RABELO; AMARAL, SANDRA LIA. Physical Training vs. Perindopril Treatment on Arterial Stiffening of Spontaneously Hypertensive Rats: A Proteomic Analysis and Possible Mechanisms. BIOMEDICINES, v. 11, n. 5, p. 17-pg., . (19/26117-8, 19/26070-1, 19/25603-6)

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