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

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.