Hydrogen Sulfide Treatment Promotes Glucose Uptake by Increasing Insulin Receptor Sensitivity and Ameliorates Kidney Lesions in Type 2 Diabetes

Abstract

Aims: To examine if hydrogen sulfide (H₂S) can promote glucose uptake and provide amelioration in type 2 diabetes. Results: Treatment with sodium hydrosulfide (NaHS, an H₂S donor) increased glucose uptake in both myotubes and adipocytes. The H₂S gas solution showed similar effects. The NaHS effects were blocked by an siRNA-mediated knockdown of the insulin receptor (IR). NaHS also increased phosphorylation of the IR, PI3K, and Akt. In Goto-Kakizaki (GK) diabetic rats, chronic NaHS treatment (30 μmol·kg⁻¹·day⁻¹) decreased fasting blood glucose, increased insulin sensitivity, and increased glucose tolerance with increased phosphorylation of PI3K and Akt in muscles. Similar insulin-sensitizing effects of NaHS treatment were also observed in Wistar rats. Moreover, glucose uptake was reduced in the cells with siRNA-mediated knockdown of the H₂S-generating enzyme cystathionine γ-lyase in the presence or absence of exogenous H₂S. Moreover, chronic NaHS treatment reduced oxygen species and the number of crescentic glomeruli in the kidney of GK rats. Innovation and Conclusion: This study provides the first piece of evidence for the insulin-sensitizing effect of NaHS/H₂S in the both in vitro and in vivo models of insulin resistance. Rebound Track: This work was rejected during a standard peer review and rescued by the Rebound Peer Review (Antoxid Redox Signal 16: 293–296, 2012) with the following serving as open reviewers: Jin-Song Bian, Samuel Dudley, Hideo Kimura, and Xian Wang. Antioxid. Redox Signal. 19, 5–23.