Effect of physical exercise on modulation of peroxisome proliferator-activated receptor ³ (PPAR³) and insulin-degrading enzyme (IDE) in the pancreatic islet of mice

• Grant number: 17/06475-1
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: July 01, 2017
• End date: March 11, 2018
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Agreement: 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
• Associated research grant: 15/12611-0 - Molecular mechanisms involved in pancreatic beta cell disfunction and dead in diabetes mellitus: strategies for the inhibition of these processes and restoration of the insular mass, AP.TEM

Abstract

PPAR³ agonists increase the insulin sensitivity and are used in the treatment of type 2 diabetes mellitus (T2DM). In pancreatic islets, PPAR³ controls insulin secretion, oxidative stress, SR stress and amyloid formation. It is known that the insulin-degrading enzyme (IDE) is the main responsible for the degradation of islet amyloid polypeptide (IAPP), reducing the amyloid 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 this enzyme could mediate some of the beneficial effects of PPAR³ in these cells. In addition, physical exercises, recommended to T2DM 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 (INS1E), will be distributed in the following groups: control group (CTL) and a group treated with rosiglitazone, which is a PPAR³ agonist (RZG). 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 and ² cells line. For this, isolated islets and INS1E cells will be distributed into the following groups: CTL, RZG, and a group treated with rosiglitazone + ML345, an IDE inhibitor (RZG+ML). Insulin secretion, islet cells survival, IAPP degradation and amyloid 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, a PPAR³ antagonist (TRE+GW). Insulin secretion, islet cell survival, IAPP degradation, amyloid formation, and the gene and protein expression (Real-time RT-PCR, and Western blot, respectively) of PPAR³ and IDE will be measured. (AU)

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.; 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, JUN 2019. (17/06475-1, 15/12611-0, 14/24719-7)

MARMENTINI, CARINE; SOARES, GABRIELA M.; BRONCZEK, GABRIELA A.; PIOVAN, SILVANO; MAREZE-COSTA, CECILIA E.; CARNEIRO, EVERARDO M.; BOSCHERO, ANTONIO C.; KURAUTI, MIRIAN A.. Aging Reduces Insulin Clearance in Mice. FRONTIERS IN ENDOCRINOLOGY, v. 12, MAY 12 2021. (15/12611-0, 18/24368-0, 13/07607-8, 17/06475-1)