L‐Cysteine supplementation lowers blood glucose, CRP, MCP‐1 and inhibits NFkB and Akt activation in liver of Zucker diabetic rats

Abstract

Many proteins, including insulin contain free sulfhyryl groups that are considered to be pivotal for their biological functions. L‐Cysteine is a semi‐essential amino acid with a free sulfhyryl group. This study examined the hypothesis that L‐cysteine supplementation can lower insulin resistance, glycemia and markers of vascular inflammation in type 2 diabetes using Zucker diabetic fatty (ZDF) rats.Starting at the age of 6 wks, ZDF rats were supplemented orally (daily gavages for 8 more wks) with saline‐placebo (D) or L‐cysteine (LC, 1mg/KgBW), and fed with a high calorie diet. ZDF rats of 6 wks age without any supplementations were considered as baseline (BL). Blood was collected by heart puncture using anesthesia from BL, D and LC supplemented rats.D rats showed elevated levels of fasting blood glucose, HbA1, CRP, MCP‐1, when compared to BL rats where there is no onset of diabetes. LC supplementation significantly lowered blood glucose (18%, p=0.05), HbA1 (8%, p=0.02), CRP (23%, p=0.02), MCP‐1 (32%, p=0.01) and HOMA index of insulin resistance (25%) when compared to D. There were no changes in blood GSH and lipid peroxidation levels between D and LC. While LC did not change blood hematocrit or levels of transaminases, however it did lower alkaline phosphatase (29%, p=0.01) levels in comparison to D. Western blotting analyses of liver showed increased activation of NFkB (50% pNFkB) and Akt (20%, pAkt) in D when compared with BL. LC supplementation reversed these effects (17% pAKT, 18% pNFkB). Thus, L‐cysteine supplementation can lower glycemia and markers of vascular inflammation, apparently by preventing NFkB activation, in ZDF rats.