Effect of Lorsatan on the functionality and palmitate-induced superoxide production in INS1-E cells

• Grant number: 21/10239-7
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): December 01, 2021
• Effective date (End): November 30, 2022
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Aparecida Emiko Hirata
• Grantee: Beatriz Lemos Felismino da Silva
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

It's known that the glucose-induced insulin secretion can be followed by the increase of reactive oxygen species (ROS) which can partly be attributed to the action of the NAD(P)H oxidase enzyme. It has been demonstrated that pancreatic islet cells express the components of NAD(P)H oxidase, which takes part in the insulin secretion process induced by glucose. Many studies have been demonstrating that high concentrations of glucose (glucotoxicity) and fatty acids (lipotoxicity) impair the pancreatic cell's functionality by mechanisms that involve ROS generation, suggesting that this might be one of the determining factors to the development of diabetes. Multiple clinical studies have shown that hypertensive subjects treated with the Angiotensin II and/or the Angiotensin-Converting Enzyme (ACE) inhibitors, reduce the risk of new-onset diabetes when compared to treatment with other antihypertensive agents. It's also known that Ang II, through its receptor AT1, it's able to stimulate NAD(P)H oxidase enzyme and that the production of ROS, antagonizes the insulin effects. Thus, the goal of this project is to assess the effect that Lorsatan has on the functionality and palmitate-induced superoxide production in INS1-E cells. (AU)