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

Abstract

Diabetic patients have lower blood concentration of H2S. Recent studies reveal several physiological roles of H2S, including vasodilator, antioxidant, anti-inflammatory and anti-atherosclerotic effects in in vitro and animal studies. This study examined the hypothesis that supplementation with L-cysteine, an endogenous precursor of H2S, replenishes blood levels of H2S and lowers insulin resistance and vascular inflammation markers in type 2 diabetes using Zucker diabetic rats (ZDF) rats as a model. Starting at age of 6 wks, ZDF rats were supplemented orally (daily gavages, 8 wks) with saline-placebo (D, n=8) or L-cysteine (LC, n=12, 1 mg/KgBW) and fed a high calorie diet. 6 weeks age rats without any supplementation were considered baseline (BL) rats. Fasting blood levels of D rats showed lower H2S, and elevated GHb, MCP-1 and insulin resistance when compared with BL 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-α (31%) and HOMA insulin resistance (25%) compared with levels seen in salinesupplemented D. The blood levels of GHb and IR showed a significant negative correlation (p<0.05) with concentrations of H2S and nitrite in LC supplemented ZDF rats. This is the first report showing L-cysteine supplementation can increase circulating levels of H2S and NO2 in a diabetic animal model, and needs to be explored as an adjuvant therapy for the reduction of vascular inflammation in the diabetic patient population.