Illustrating the mechanism by which small molecule stabilizers of the ChREBP?/14-3-3 protein-protein interaction (PPI) protect insulin-secreting beta cells from glucolipotoxicity. The optimized "molecular glue" compounds retain ChREBP? in the cytoplasm, preventing its transcriptional activity and subsequent beta cell dedifferentiation and death. This approach highlights a novel therapeutic strategy for maintaining beta cell identity and function in the context of type 2 diabetes.
Findings could improve long-term outcomes for patients
Researchers from the Icahn School of Medicine at Mount Sinai in New York have discovered a novel approach to protecting insulin-producing beta cells from the damaging effects of glucolipotoxicity—a harmful condition linked to the progression of type 2 diabetes (T2D). These findings, published on March 2, 2025 in Nature Communications, could lead to promising treatments targeting beta cell dysfunction.