L-cysteine supplementation lowers blood glucose, glycated hemoglobin, CRP, MCP-1, and oxidative stress and inhibits NF-kappaB activation in the livers of Zucker diabetic rats

Free Radic Biol Med. 2009 Jun 15;46(12):1633-8. doi: 10.1016/j.freeradbiomed.2009.03.014. Epub 2009 Mar 26.

Abstract

This study examined the hypothesis that l-cysteine supplementation can lower insulin resistance, glycemia, oxidative stress, and markers of vascular inflammation in type 2 diabetes using Zucker diabetic fatty (ZDF) rats as a model. Starting at the age of 6 weeks, ZDF rats were supplemented orally (daily gavage, 8 weeks) with saline placebo (D) or l-cysteine (LC; 1 mg/kg bw) and fed a high-calorie diet. Six-week-old rats without any supplementation were considered baseline (BL) rats. D rats showed elevated fasting blood glucose, glycated Hb, CRP, and MCP-1 compared with BL rats in which there was no onset of diabetes. LC supplementation significantly lowered blood levels of glucose (18%, p= 0.05), glycated Hb (8%, p= 0.02), CRP (23%, p= 0.02), MCP-1 (32%, p= 0.01), and insulin resistance (25%) compared with levels seen in saline-supplemented D rats. There was a decrease in plasma protein oxidation levels (p< 0.01); however, GSH levels were similar in LC and D groups. Although LC did not change blood hematocrit or levels of transaminases, it did lower alkaline phosphatase (29%, p= 0.01) levels in comparison to D. Western blotting analyses of liver showed increased activation of NF-kappaB and Akt (50% pNF-kappaB and 20% pAkt) in D compared with BL rats. LC supplementation inhibited these effects (17% pAkt, 18% pNF-kappaB). This is the first report showing that l-cysteine supplementation can lower glycemia and markers of vascular inflammation in diabetes apparently by preventing NF-kappaB activation in a diabetic animal model.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Administration, Oral
  • Animals
  • Blood Glucose / drug effects*
  • Carrier Proteins / blood*
  • Chemokine CCL2 / blood*
  • Cysteine / administration & dosage
  • Cysteine / pharmacology*
  • Diabetes Mellitus, Experimental / blood
  • Diabetes Mellitus, Experimental / drug therapy
  • Diabetes Mellitus, Experimental / metabolism*
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / drug therapy
  • Diabetes Mellitus, Type 2 / metabolism
  • Dietary Supplements
  • Disease Models, Animal
  • Free Radicals / administration & dosage
  • Free Radicals / pharmacology
  • Glycated Hemoglobin A / metabolism*
  • Insulin / blood
  • Liver / drug effects
  • Liver / metabolism
  • Male
  • NF-kappa B / antagonists & inhibitors*
  • NF-kappa B / metabolism
  • Oxidative Stress / drug effects*
  • Phosphorylation
  • Proto-Oncogene Proteins c-akt / antagonists & inhibitors
  • Proto-Oncogene Proteins c-akt / metabolism
  • Rats
  • Rats, Zucker

Substances

  • Blood Glucose
  • Carrier Proteins
  • Ccl2 protein, rat
  • Chemokine CCL2
  • Crp protein, rat
  • Free Radicals
  • Glycated Hemoglobin A
  • Insulin
  • NF-kappa B
  • Proto-Oncogene Proteins c-akt
  • Cysteine