Dihydrolipoic acid improves diabetic endothelial cell function via the H₂S-producing enzyme 3-mercaptopyruvate...

High glucose-induced endothelial dysfunction is a hallmark of diabetic microvascular complications. Reduced hydrogen sulphide (H₂S) levels and dysregulation of the H₂S-producing enzyme 3-mercaptopyruvate sulfurtransferase (3-MST) are linked to this dysfunction. Dihydrolipoic acid (DHLA), formed from alpha-lipoic acid in mitochondria, has been proposed to enhance H₂S release from 3-MST; however, this has not been empirically tested in diabetes. Using a cell culture model, this study demonstrates that DHLA supplementation enhances H₂S production via 3-MST and improves endothelial function under high glucose conditions. Our results provide foundational knowledge and indicate that targeting the 3-MST/H₂S pathway via DHLA supplementation may have therapeutic potential to reduce or slow the onset and progression of diabetic microvascular complications.