Project R-16093

MOTS-c in the Peloton of Exerkines: A Breakthrough for Vascular Health in Type 2 Diabetes (Research)

Type 2 diabetes (T2DM) is a global health challenge, with current treatments focusing on glycemic control but with less focus on vascular dysfunction, a major driver of diabetes-related complications. MOTS-c, a mitochondrial-derived peptide and exercise-induced exerkine, has emerged as a promising metabolic regulator, yet its role in endothelial health remains unclear. I hypothesize that MOTS-c enhances endothelial nitric oxide availability, reduces oxidative stress, and mitigates inflammation, thereby improving macro- and microvascular function in T2DM. To test this, I will (1) assess the effects of MOTS-c treatment on endothelial and vascular function using in vitro models and a novel T2DM rat model, and (2) examine whether moderate-intensity endurance exercise training increases circulatory MOTS-c levels, promoting vascular protection in both a T2DM rat model and a case-control study with T2DM patients. Using advanced techniques, including Seahorse metabolic analysis, aortic ring assays, and light-sheet microscopy, this project will provide mechanistic insights into MOTS-c's vascular benefits, paving the way for mitochondria-targeted therapies. By addressing this critical gap in T2DM management, this research can potentially improve diabetes care and patient outcomes.

01 November 2025 - 31 October 2029