L-cysteine Supplementation Increases Blood Levels of Hydrogen Sulfide and Nitrite, and Decreases Insulin Resistance and Vascular Inflammation in Zucker Diabetic Rats

Abstract

Abstract Objectives Diabetic patients have lower blood levels of hydrogen sulfide (H2S). H2S has potent antioxidant, anti-inflammatory and anti-atherosclerotic effects in vitro and in animal studies. This study examined the hypothesis that supplementation with L-cysteine, an endogenous precursor of H2S increases blood levels of H2S and lowers insulin resistance and vascular inflammation biomarkers in type 2 diabetes using Zucker diabetic (ZDF) rats as a model. Methods Starting at age of 6 weeks, ZDF rats were supplemented orally, daily gavages for 8 weeks with saline-placebo (D, n = 8) or L-cysteine (LC, n = 12, 1 mg/kg BW) and fed a high calorie diet. 6 weeks age rats without any supplementation were considered baseline (BL) rats. Results Fasting blood levels of D rats showed lower H2S and elevated HGb, MCP-1 and insulin resistance when compared with baseline in which there was no onset of diabetes. LC supplementation significantly (P < 0.05) increased blood levels of H2S (37%), and NO2 (30%) and lowered levels of GHb (9%), MCP-1 (31%), TNF (31%) and HOMA insulin resistance (25%) compared with levels seen in saline supplemented D. The blood levels of GHb and IR showed a significant correlation (P < 0.05) with concentrations of H2S and nitrite in LC-supplemented ZDF rats. Conclusions This shows that L-cysteine supplementation can increase levels of H2S and NO2 in diabetic animal model, and needs to be validated as an adjuvant therapy for the reduction of vascular inflammation and insulin resistance in the diabetic patient population. Funding Sources This study was supported by the NCCIH.