Control of DNA methylation of pancreatic islet through a crosstalk mechanism with the skeletal muscle cells

• Grant number: 18/11060-8
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Start date: July 30, 2018
• End date: March 29, 2019
• Field of knowledge: Biological Sciences - Physiology - Physiology of Effort
• Principal Investigator: Antonio Carlos Boschiero
• Grantee: José Maria Costa Júnior
• Supervisor: Charlotte Ling
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Institution abroad: Lund University, Malmö, Sweden
• Associated to the scholarship: 16/17102-9 - Function of myostatin in epigenetic control of pancreatic beta cells proliferation, BP.PD

Abstract

Pancreatic beta cell failure is crucial to type 2 diabetes (T2-D) developments. The insulin resistance in the peripheral tissues is usually linked to this phenomenon. However, most of insulin-resistant obese people do not develop T2-D. It indicates an important role of genetic susceptibility in this context. Nevertheless, less than 10% of genetic variants are associated to the disease. In this sense, the environment factors via epigenetic regulation emerge as an important mechanism in this context. In fact, pancreatic islets from T2-D subjects are hypermethylated in several key genes involved in beta cell function, compared to healthy donors. Physical exercise improves the pancreatic beta cell function of T2-D and T1-D subjects. A crosstalk between the skeletal muscle and pancreas orchestrated by myokines seems to be involved. However, the possible alteration that exercise could induces to the epigenome in pancreatic islet remains unknown. In this way, we aim to use human skeletal muscle cells obtained before and after a single bout of endurance exercise, as well as human pancreatic islet to explore via conditioned medium approach, the possible involvement of myokines as modulators of the epigenetic mechanism in the human pancreatic islets. (AU)