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