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Effect of physical exercise on the expression of peroxisome proliferator activated receptor gamma (PPARgamma) and Insulin Degrading Enzyme (IDE) in mouse pancreatic islets

Grant number: 14/24719-7
Support Opportunities:Scholarships in Brazil - Doctorate
Effective date (Start): March 01, 2015
Effective date (End): June 30, 2017
Field of knowledge:Biological Sciences - Physiology - Physiology of Organs and Systems
Acordo de Cooperação: Coordination of Improvement of Higher Education Personnel (CAPES)
Principal Investigator:Antonio Carlos Boschiero
Grantee:Mirian Ayumi Kurauti
Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil


PPAR³ agonists increase the insulin sensitivity and are used in the treatment of DM2. In pancreatic islets, PPAR³ controls: insulin secretion, oxidative stress, SR stress, and amiloid formation. It is known that the insulin degrading enzyme (IDE) is the (main) responsible for the degradation of IAPP, reducing the amiloid formation. Based on the fact that PPAR³ increases the expression of IDE in neuronal tissues and hepatocytes, we thought that PPAR³ may control IDE expression, also in pancreatic ² cells, and IDE could mediate some of the beneficial effects of PPAR³ in these cells. In addition, physical exercises, recommended to DM2 patients, also modulate the expression of PPAR³ in various tissues. Thus, our second hypothesis is that physical exercise could also interfere in the expression of PPAR³ in pancreatic islets and, as a consequence, PPAR³ could control the expression of IDE in this animal model. To test our first hypothesis, isolated pancreatic islets from C57BL6 mice, as well as tumoral ² cells (MIN6), will be distributed in the following groups: control (CTL), treated with rosiglitazone (PPAR³ agonist) (RZG), and treated with GW9662 (PPAR³ antagonist) (GW). After the treatment, the expression of IDE will be assessed. If the effect of PPAR³ upon the expression of IDE is confirmed, we will analyze if IDE modulates the effects of PPAR³ in the islets. For this, isolated islets and MIN6 cells will be distributed into the following groups: CTL, RZG, and treated with rosiglitazone + bacitracin, an IDE inhibitor (RZG+BAC). Insulin secretion, islet cells survival, IAPP degradation and amiloid formation will be measured. To test if exercise regulates the expression of PPAR³, mice will be distributed in control (CTL) and exercised groups (mice trained in a treadmill 5 days a week for 1 hour during two months) (TRE). After this period, the mice will be euthanized and their islets distributed in the following groups: control (CTL), exercised (TRE), and exercised treated with GW9662 (TRE+GW). Insulin secretion, islet cell survival, IAPP degradation, amiloid formation, and the gene and protein expression (Real-time RT-PCR, and Western blot, respectively) of PPAR³ and IDE will be measured. (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)
KURAUTI, MIRIAN A.; COSTA-JUNIOR, JOSE M.; FERREIRA, SANDRA M.; SANTOS, GUSTAVO J.; SPONTON, CARLOS H. G.; CARNEIRO, EVERARDO M.; TELLES, GUILHERME D.; CHACON-MIKAHIL, MARA P. T.; CAVAGLIERI, CLAUDIA R.; REZENDE, LUIZ F.; et al. Interleukin-6 increases the expression and activity of insulin-degrading enzyme. SCIENTIFIC REPORTS, v. 7, . (15/12611-0, 14/24719-7)
KURAUTI, MIRIAN A.; FERREIRA, SANDRA M.; SOARES, GABRIELA M.; VETTORAZZI, JEAN F.; CARNEIRO, EVERARDO M.; BOSCHERO, ANTONIO C.; COSTA-JUNIOR, JOSE M.. Hyperinsulinemia is associated with increasing insulin secretion but not with decreasing insulin clearance in an age-related metabolic dysfunction mice model. Journal of Cellular Physiology, v. 234, n. 6, p. 9802-9809, . (17/06475-1, 15/12611-0, 14/24719-7)
KURAUTI, MIRIAN A.; FREITAS-DIAS, RICARDO; FERREIRA, SANDRA M.; VETTORAZZI, JEAN F.; NARDELLI, TARLLIZA R.; ARAUJO, HYGOR N.; SANTOS, GUSTAVO J.; CARNEIRO, EVERARDO M.; BOSCHERO, ANTONIO C.; REZENDE, LUIZ F.; et al. Acute Exercise Improves Insulin Clearance and Increases the Expression of Insulin-Degrading Enzyme in the Liver and Skeletal Muscle of Swiss Mice. PLoS One, v. 11, n. 7, . (13/07607-8, 14/24719-7)
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
KURAUTI, Mirian Ayumi. The role of interleukin-6 (IL-6) on the modulation of insulin-degrading enzyme (IDE) during the acute exercise. 2017. Doctoral Thesis - Universidade Estadual de Campinas (UNICAMP). Instituto de Biologia Campinas, SP.

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