Investigation of the effects of gondoic acid on the insulin secretion from pacreatic islets

• Grant number: 24/18265-5
• Support Opportunities: Scholarships in Brazil - Program to Stimulate Scientific Vocations
• Start date: February 17, 2025
• End date: March 31, 2025
• Field of knowledge: Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
• Principal Investigator: Luiz Osório Silveira Leiria
• Grantee: Nicolas Sa Rodrigues Maia
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Obesity is a pandemic with increasing prevalence and is a major independent risk factor for type 2 diabetes development and many other diseases. Insulin resistance can be observed in the early stages of obesity induced type 2 diabetes. Increased level of circulating insulin is usually noticed before hyperglycemia. Indeed, it can be observed two weeks after a high fat diet challenge. Hyperinsulinemia itself can contribute to many obesity-derived comorbidities and increase adiposity. On the other hand, lipolysis of the adipose tissue is strongly regulated by insulin and seen to be one of the first pathways affected by insulin resistance. There is evidence supporting the idea that lipolysis of adipose tissue can increase insulin secretion by releasing free fatty-acids capable of stimulating beta-cells. In our lab we found that adipocyte-conditional deletion of the rate limiting enzyme for the lipolytic cascade, ATGL, rendered mice with a protection against the hyperinsulinemia induced by high fat diet. We observed through a lipidomic study held in plasma from those mice that godocic acid was the only free fatty acid that was increased in obese mice while it was lower in the Atgl knockout mice, indicating that this lipid may act as a mediator of the early onset hyperinsulinemia under high fat diet, thus link adipose tissue lipolysis with insulin secretion. With these data in mind, our goal is to investigate whether and how gondoic acid directly promotes insulin secretion from beta cells, using isolated pancreatic islets in culture. (AU)