Effects of intracellular peptides on bioenergetics and mitochondrial dynamics of pancreatic beta cells under lipotoxicity

• Grant number: 25/11388-7
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: August 01, 2025
• End date: July 31, 2026
• Field of knowledge: Health Sciences - Pharmacy
• Principal Investigator: Eloisa Aparecida Vilas Boas
• Grantee: Lucas Victor da Silva
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Diabetes mellitus (DM) is a chronic disease characterized by hyperglycemia that, when not treated adequately, can lead to a series of complications and a decrease in the quality and life expectancy of patients. One of the main types of DM is DM type 2 (DM2), which is closely related to obesity and metabolic syndrome. During the progression of DM2, the exposure of beta cells to high concentrations of glucose and fatty acids, especially saturated ones, leads to alterations in mitochondrial dynamics, resulting in progressive impairment of mitochondrial function, low ATP production, and high production of reactive oxygen species. Some current research focuses on understanding the intracellular mechanisms that lead to this dysfunction and death of beta cells during the establishment of DM2, and seeks new forms of treatment. In this context, intracellular peptides have shown promise, with preliminary evidence of positive effects on energy metabolism and mitochondrial function, although their impacts on pancreatic beta cells have not yet been explored. Through partnerships, this project aims to evaluate the effect of selected intracellular peptides from a previous screening on mitochondrial dysfunction and beta cell death in a lipotoxicity model, which simulates DM2. For this purpose, a pancreatic beta cell line (BRIN-BD11) will be used, which will be exposed to palmitic acid (a condition that mimics DM2) in the presence or absence of pre-selected intracellular peptides in previous studies. From there, possible protective effects of the peptides on the changes induced by palmitic acid will be evaluated, including changes in cell morphology, viability and cell proliferation, mitochondrial oxygen consumption (using the Seahorse Extracellular Flux Analyzer equipment), protein expression of mitochondrial complexes, as well as the expression of markers related to mitochondrial dynamics (fusion and fission) and mitochondrial biogenesis. Therefore, this project aims to understand the role of intracellular peptides in an experimental model of DM2, in addition to contributing to the discussion about new therapeutic approaches based on peptidic molecules for the treatment of DM2.