title: Vitamin D and L-cysteine levels correlate positively with GSH and negatively with insulin resistance levels in the blood of type 2 diabetic patients.
abstract: OBJECTIVE
  Vitamin D, L-cysteine (LC) and glutathione (GSH) levels are lower in the blood of diabetic patients. This study examined the hypothesis that the levels of vitamin D and LC correlate with those of GSH in the blood of type 2 diabetic patients (T2D), and that vitamin D and LC upregulate glutamate-cysteine ligase (GCLC), which catalyzes GSH biosynthesis, in cultured monocytes.
  
  
  METHODS
  Fasting blood was obtained after written informed consent from T2D (n=79) and healthy controls (n=22). U937 monocytes were pretreated with 1,25 (OH)2 vitamin D (0-25 nM) or LC (0-500 μM) for 24 h and then exposed to control or high glucose (25 mM) for 4 h.
  
  
  RESULTS
  Plasma levels of vitamin D, LC, GSH and GCLC protein were significantly lower in T2D versus those in age-matched healthy controls. Multiple linear regression analyses and adjustment for body weight showed a significant positive correlation between plasma levels of vitamin D (r=0.26, P=0.05) and LC (r=0.81, P=0.001) and that of GSH, and between LC and vitamin D (r=0.27, P=0.045) levels. Plasma levels of GSH (r=-0.34, P=0.01) and LC (r=-0.33, r=0.01) showed a negative correlation with triglyceride levels. Vitamin D correlated inversely with HbA1C (-0.30, P=0.01) and homeostatic model assessment insulin resistance (r=-0.31, P=0.03), which showed a significant positive correlation with triglycerides (r=0.44, P=0.001) in T2D. Cell culture studies demonstrate that supplementation with vitamin D and LC significantly increased GCLC expression and GSH formation in control and high-glucose-treated monocytes.
  
  
  CONCLUSIONS
  This study suggests a positive relationship between the concentrations of the micronutrients vitamin D and LC and that of GSH. Some of the beneficial effects of vitamin D and LC supplementation may be mediated by an increase in the levels of GSH and a decrease in triglyceride levels in T2D patients.
authors: Department of Pediatrics, Louisiana State University Health Sciences Center, Shreveport, LA, USA.
authors: S K
authors: SK
authors: Jain
authors: Department of Pediatrics, Louisiana State University Health Sciences Center, Shreveport, LA, USA.
authors: D
authors: D
authors: Micinski
authors: Department of Pediatrics, Louisiana State University Health Sciences Center, Shreveport, LA, USA.
authors: L
authors: L
authors: Huning
authors: Department of Medicine, Louisiana State University Health Sciences Center, Shreveport, LA, USA.
authors: G
authors: G
authors: Kahlon
authors: Department of Medicine, Louisiana State University Health Sciences Center, Shreveport, LA, USA.
authors: P F
authors: PF
authors: Bass
authors: Department of Medicine, Louisiana State University Health Sciences Center, Shreveport, LA, USA.
authors: S N
authors: SN
authors: Levine
mesh_terms: D002460:Cell Line; D003545:Cysteine / Q000097:blood* / Q000494:pharmacology; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D019587:Dietary Supplements; D005260:Female; D005721:Glutamate-Cysteine Ligase / Q000494:pharmacology; D005978:Glutathione / Q000096:biosynthesis / Q000097:blood*; D006801:Humans; D007328:Insulin / Q000097:blood / Q000378:metabolism; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000201:enzymology; D018384:Oxidative Stress / Q000187:drug effects; D014280:Triglycerides / Q000097:blood; D014807:Vitamin D / Q000097:blood* / Q000494:pharmacology
chemical_list: D007328:Insulin; D014280:Triglycerides; D014807:Vitamin D; D005721:Glutamate-Cysteine Ligase; D005978:Glutathione; D003545:Cysteine