IMPACT OF SGLT2 INHIBITION ON THE REGULATION OF SIRTUINS, INFLAMMATION, AND IONIC HOMEOSTASIS IN THE HEART AND KIDNEY OF TYPE 1 DIABETES MELLITUS MODEL

• Grant number: 25/01021-9
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: September 01, 2025
• End date: August 31, 2026
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Elida Paula Benquique Ojopi
• Grantee: Alexandre Dias Muniz
• Host Institution: Hospital das Clínicas da Faculdade de Medicina de Botucatu. Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

Type 1 diabetes mellitus (T1DM) is a chronic condition associated with metabolic alterations and damage to multiple organs and systems, including cardiovascular complications such as diabetic cardiomyopathy. In the heart, it is linked to diabetic cardiomyopathy, characterized by structural and functional cardiac changes not attributed to hypertension, coronary artery disease, or valvular disorders. Initially asymptomatic, this condition progresses from myocardial stiffness and diastolic dysfunction to heart failure with preserved or reduced ejection fraction.SGLT2 inhibitors (gliflozins), initially introduced as antidiabetic agents, have demonstrated benefits beyond glycemic control, including the reduction of cardiovascular events in patients with type 2 diabetes. Evidence suggests that these benefits may be associated with mechanisms independent of glycemia, including the regulation of ionic homeostasis and modulation of inflammatory and oxidative pathways.This study investigates the effects of dapagliflozin, an SGLT2 inhibitor, on the regulation of genes related to sirtuins (Sirt1, Sirt3, and Sirt6), inflammation (Il1b and Il6), and cardiac ionic homeostasis (Nhe1 and Ncx) in streptozotocin-induced T1DM rats. Male Wistar rats were divided into the following groups: control (C, n=20), control treated with dapagliflozin (C-Dapa, n=20), diabetic (D, n=20), and diabetic treated with dapagliflozin (DM-Dapa, n=20).This work provides new insights into the therapeutic potential of these drugs in addressing cardiovascular complications in T1DM. (AU)