Intracellular glutathione production, but not protein glycation, underlies the protective effects of captopril against 2-deoxy-D-ribose-induced β-cell damage.

Our previous study reported that both oxidative stress and protein glycation were the principal mechanisms underlying 2‑deoxy‑D‑ribose (dRib)‑induced pancreatic β‑cell damage. The aim of the present study was to investigate the effects of captopril on dRib‑induced damage in pancreatic β‑cells, as well as to determine the mechanisms underlying these effects. Treatment with dRib increased the levels of cytotoxicity, apoptosis, and intracellular reactive oxygen species in Syrian hamster insulinoma HIT‑T15 cells; however, pretreatment with captopril significantly inhibited the effects of dRib. The intracellular levels of reduced and oxidized glutathione were depleted following treatment with dRib; however, these levels were restored following HIT‑T15 cell treatment with captopril. In rat islets, dRib stimulation suppressed the mRNA expression levels of insulin, and pancreatic and duodenal homeobox 1, as well as insulin content; however, these effects were dose‑dependently reversed by treatment with captopril. Treatment with buthionine sulfoximine, an inhibitor of intracellular glutathione biosynthesis, inhibited the protective effects of captopril on dRib‑mediated glutathione depletion and cytotoxicity in HIT‑T15 cells. Following incubation with albumin, dRib increased the formation of dicarbonyl and advanced glycation end products. Treatment with captopril did not inhibit the dRib‑induced increase in production of dicarbonyl and advanced glycation end products. In conclusion, treatment with captopril reversed dRib‑induced oxidative damage and suppression of insulin expression in β‑cells. The mechanism underlying the protective effects of captopril may involve increased intracellular glutathione production, rather than protein glycation.