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Does the elevation of irisin induced by physical exercise contribute to renal protection in experimental Diabetes?

Grant number: 20/14717-8
Support Opportunities:Scholarships in Brazil - Scientific Initiation
Effective date (Start): February 01, 2021
Effective date (End): March 31, 2022
Field of knowledge:Health Sciences - Medicine
Principal Investigator:Jose Butori Lopes de Faria
Grantee:Beatriz Vareda
Host Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
Associated research grant:14/22687-0 - Contribution of AMPK pathway to renal fibrosis and pathogenesis of diabetic nephropathy and retinopathy, AP.TEM

Abstract

Diabetic nephropathy (DN) is a serious and frequent complication in individuals with diabetes mellitus (DM). Clinical studies suggest that physical exercise is able to prevent and improve kidney disease in individuals with DM. Recent observations suggest that irisin, a myocin produced by muscle and stimulated by physical exercise, may be the link between muscle tissue and kidneys in renal protection induced by physical exercise, in a model of non-diabetic renal fibrosis. Whether irisin contributes to the nephroprotection of physical exercise in DM remains to be determined.Objectives: To investigate whether the elevation of irisin induced by physical exercise contributes to renal protection in experimental diabetes.Material and methods: Male Wistar mices at 8 weeks of age will be made diabetic by intravenous injection of streptozotocin (60 mg / kg). Control mices will receive the streptozotocin vehicle, citrate buffer, pH 4.5. Mices with fasting blood glucose greater than 270 mg / dl will be randomized to the following groups: sedentary diabetics, exercised diabetics (submitted to an aerobic exercise program, 5 times a week), exercised diabetics and treated with the receptor inhibitor irisin (alpha V integrin, CycloRDGyK® Selleckckem) and sedentary diabetics and treated with CycloRDGyK®, for 8 weeks. Systolic blood pressure and blood glucose will be determined every 4 weeks. Albuminuria will be determined by ELISA after 8 weeks. After the euthanasia of the mices, blood will be collected to determine plasma irisin (ELISA) and the kidneys will be removed to estimate the expression of extracellular matrix components and proteins related to Western blot inflammation, immunofluorescence and immunohistochemistry.Expected results: It is expected that in the group exercised and treated with the integrin receptor blocker, there will be no renal protection induced by physical exercise, suggesting that irisin is the mediator of renal protection in DM.

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