ANNEXIN A1 AND DIABETES: EXPLORING ITS SYSTEMIC EFFECTS IN AN EXPERIMENTAL MURINE MODEL

• Grant number: 24/18571-9
• Support Opportunities: Regular Research Grants
• Start date: November 01, 2025
• End date: April 30, 2028
• Field of knowledge: Biological Sciences - Morphology - Histology
• Principal Investigator: Cristiane Damas Gil
• Grantee: Cristiane Damas Gil
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated researchers: Adriana Degrossoli ; Andréia de Melo Porcari ; Patricia Daniele Azevedo Lima ; Samara Urban de Oliva

Abstract

Diabetes mellitus (DM) is a global public health issue that leads to systemic dysregulation, causing neurological, cardiovascular, renal, and ocular complications. Hyperglycemia in DM induces mitochondrial dysfunction and increases superoxide production, activating pathological pathways linked to these complications. As DM cases rise, we must deepen our understanding of its mechanisms to develop more effective therapies. Annexin A1 (ANXA1) emerges as a relevant protein, playing roles in inflammatory, immunological, endocrine, and tissue regeneration processes. Although elevated ANXA1 levels have been observed in DM patients and its role in insulin secretion is established, further investigations are needed to elucidate how this endogenous protein influences the systemic complications of diabetes, including its response to oxidative stress. Therefore, we will evaluate the role of ANXA1 in the systemic effects of DM using an experimental murine model. Wild-type and ANXA1 knockout mice will be subjected to the streptozotocin-induced DM1 model. Ninety days post-induction, various organs, and tissues will be collected for evaluation using multiple methodologies: morphological analyses, immunohistochemistry, immunofluorescence, oxidative stress assays, multiplex with magnetic beads, mitochondrial damage assessment, and metabolomics, among others. This study will advance the knowledge of ANXA1's role in the systemic complications of DM, focusing on molecular mechanisms involving oxidative stress and mitochondrial dysfunction, aiming to identify novel therapeutic targets for disease control and prevention. (AU)