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L‐Cysteine supplementation lowers blood glucose, CRP, MCP‐1 and inhibits NFkB and Akt activation in liver of Zucker diabetic rats
Author(s) -
Jain Sushil K.,
Velusamy Thirunavukkarasu,
Rains Justin,
Croad J L,
Bull R
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.345.2
Subject(s) - medicine , endocrinology , insulin resistance , diabetes mellitus , insulin , glutathione , hematocrit , protein kinase b , type 2 diabetes , chemistry , apoptosis , biochemistry , enzyme
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.