Abstract #3520

Assessment of RAGE-DIAPH1 interaction agonist induced changes to cardiac and muscle metabolites in a murine model of Type-1 Diabetes

Rajiv G Menon^1,2, Syed Hasan³, Ann Marie Schmidt³, Ravichandran Ramasamy³, and Ravinder R Regatte^1,2

¹Bernard and Irene Schwartz Center for Biomedical Imaging, Department of Radiology, New York University Grossman School of Medicine, New York, NY, United States, ²Center for Advanced Imaging Innovation and Research (CAI2R), Department of Radiology, New York University Grossman School of Medicine, New York, NY, United States, ³Department of Endocrinology, New York University Grossman School of Medicine, New York, NY, United States

Synopsis

Keywords: Endocrine, Diabetes

Motivation: Diabetes Mellitus causes systemic changes in lipids of multiple organs. Previous studies have shown that receptor for advanced glycation end products (RAGE) and its tail binding partner diaphanous 1 (Diaph1) are key mediators of metabolic changes in T1D mice.

Goal(s): To use ¹H-MRS and CSE-MRI to investigate the metabolic effects of the RAGE-DIAPH1 interaction antagonist, RAGE229, in T1D murine hearts and hind limb.

Approach: 18 mice were divided into 3 cohorts (Rage229/+db, RegDiet/+db, RegDiet/-db) and scanned using ¹H-MRS and CSE-MRI.

Results: Inhibition of RAGE-DIAPH1 interaction by RAGE229 leads to significant reduction in triglyceride levels in hearts and hind limb of T1D mice.

Impact: The results of this study set the stage for further testing of RAGE229 as potential therapeutic adjuncts in alleviating metabolic dysfunction in T1D.

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