Abstract
The aim of the present study was to investigate the potential therapeutic effects of molecular hydrogen on type 2 diabetes mellitus (T2DM) in rats. Following maintenance on a high-fat diet for 4 weeks, a T2DM model was established using an injection of 30 mg/kg streptozotocin via the caudal vein into Sprague-Dawley rats. On day 0 and Day 80, the blood samples were obtained from each rat for the measurement of biochemical indicators including blood lipids, fasting blood glucose, hepatic glycogen, fasting serum insulin, insulin sensitivity index, insulin resistance index, serum superoxide dismutase (SOD) and serum malondialdehyde (MDA) using an automatic biochemical analyzer. The kidneys and pancreas tissues were harvested for HE staining and Western blot assay of toll-like receptor 4 (TLR4), myeloid differentiation primary response 88 (MyD88), phosphorylated (p)-p65, p65, p-IκB and IκB. The results showed that in rats with T2DM, molecular hydrogen treatment decreased fasting blood glucose levels, increased hepatic glycogen synthesis and improved insulin sensitivity. Treatment with molecular hydrogen also increased the production of SOD whilst decreasing the production of MDA. In addition, molecular hydrogen alleviated the pathological changes exhibited by pancreatic islets and kidney during T2DM. Mechanistically, molecular hydrogen decreased TLR4 and MyD88 expression levels whilst also decreasing p65 and NF-κB inhibitor phosphorylation. In conclusion, molecular hydrogen exerted therapeutic effects against T2DM by improving hyperglycemia and inhibiting oxidative stress through mechanisms that are associated with the TLR4/MyD88/NF-κB signaling pathway.