Modulation of AMPK pathway by phenolic compounds from Brazilian fruits in L6 myocytes

• Grant number: 12/12012-0
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Start date: February 11, 2013
• End date: December 10, 2013
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Rui Curi
• Grantee: Camilo de Lellis Santos
• Supervisor: André Marette
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Institution abroad: Université Laval, Canada
• Associated to the scholarship: 10/10778-0 - Modulation of inflammation- and diabetes-related intracellular signalling pathways by phenolic compounds extracted from brazilian native fruits extracts, BP.PD

Abstract

Reduced glucose uptake in muscle cell triggered by insulin signalling impairment due to insulin receptor nitrosylation is a mechanism that contributes to the development of metabolic syndrome. Phenolic compounds from fruits and vegetables are likely to prevent metabolic syndrome through activation of AMPK, a protein that induces insulin-independent glucose uptake and inhibits inducible nitric oxide synthase (iNOS) activity. Although several Brazilian vegetables extracts studies have been shown antidiabetic and anti-inflammatory effects, the precise molecular mechanism of action of the compounds from those fruits is still a matter of question. The presente work aim to evaluate inhibitory effects of phenolic extracts from Brazilian fruits (Cagaita - Eugenia dysenterica DC and Araçá - Psidium catleianum Sabine) on inflammatory processes and insulin resistance in muscle and hepatic cells. Glucose uptake by L6 myocytes and hepatic glucose production by FAO cells upon extracts incubation will be analyzed. In order to identify the role of AMPK over extracts effects, a double-knockout AMPK myocytes lineage (AMPK±1-/- AMPK±2 -/-) will be used. Additionally, after caracterization of phenolic compounds content by LC-MS in the extracts, the cells will be treated with each isolated compound as well as equimolar mixture of the compounds to identify new molecules or putative bioactives mixture to treat or prevent metabolic syndrome. (AU)