Evaluation of the Effects of Mangiferin on Gluconeogenic Enzymes and the Insulin Pathway in HepG2.

• Grant number: 25/07329-5
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: June 01, 2025
• End date: May 31, 2026
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Luciana Chagas Caperuto
• Grantee: Eduarda Sant'Anna Mendes
• Host Institution: Instituto de Ciências Ambientais, Químicas e Farmacêuticas (ICAQF). Universidade Federal de São Paulo (UNIFESP). Campus Diadema. Diadema , SP, Brazil

Abstract

Diabetes Mellitus (DM) is a chronic non-communicable metabolic disease characterized by hyperglycemia due to the secretion or inefficient action of insulin. Insulin resistance (IR) impairs the signaling of this hormone and glucose uptake, resulting in an increase in blood glucose. Worldwide, DM is a public health problem with high mortality and morbidity, affecting millions of people. The global impact of DM drives the search for new safe, accessible, and effective therapeutic approaches to improve patients' quality of life. Mangiferin (MGF), a bioactive compound found in Mangifera Indica, has several pharmacological activities, including antidiabetic and hypoglycemic effects shown in previous studies. The liver and pancreas are crucial for energy metabolism. In the liver, insulin inhibits hepatic glucose production and stimulates glucose storage in the form of glycogen. In liver tissue, AMP-dependent protein kinase (AMPK) is linked with the modulation of the enzymes phosphoenolpyruvate carboxykinase (PEPCK) and glucose 6-phosphatase (G6Pase), key enzymes in the gluconeogenesis process. Alteration in the expression and/or activity of these enzymes is linked to the insulin resistance observed in T2DM. This project aims to investigate whether MGF modulates the gene and protein expression of PEPCK and G6Pase, in addition to the phosphorylation of AKT in HepG2 cells. For this purpose, cell cultures, probability tests (MTT), treatment with MGF, gene expression (RT-PCR) and protein (Western Blotting) analyses will be performed. (AU)