title: L-cysteine supplementation upregulates glutathione (GSH) and vitamin D binding protein (VDBP) in hepatocytes cultured in high glucose and in vivo in liver, and increases blood levels of GSH, VDBP, and 25-hydroxy-vitamin D in Zucker diabetic fatty rats.
abstract: Vitamin D binding protein (VDBP) status has an effect on and can potentially improve the status of 25(OH) vitamin D and increase the metabolic actions of 25(OH) vitamin D under physiological and pathological conditions. Diabetes is associated with lower levels of glutathione (GSH) and 25(OH) vitamin D. This study examined the hypothesis that upregulation of GSH will also upregulate blood levels of VDBP and 25(OH) vitamin D in type 2 diabetic rats.
  
  
  
  L-cysteine (LC) supplementation was used to upregulate GSH status in a FL83B hepatocyte cell culture model and in vivo using Zucker diabetic fatty (ZDF) rats. Results show that LC supplementation upregulates both protein and mRNA expression of VDBP and vitamin D receptor (VDR) and GSH status in hepatocytes exposed to high glucose, and that GSH deficiency, induced by glutamate cysteine ligase knockdown, resulted in the downregulation of GSH, VDBP, and VDR and an increase in oxidative stress levels in hepatocytes. In vivo, LC supplementation increased GSH and protein and mRNA expression of VDBP and vitamin D 25-hydroxylase (CYP2R1) in the liver, and simultaneously resulted in elevated blood levels of LC and GSH, as well as increases in VDBP and 25(OH) vitamin D levels, and decreased inflammatory biomarkers in ZDF rats compared with those in placebo-supplemented ZDF rats consuming a similar diet.
  
  
  
  LC supplementation may provide a novel approach by which to raise blood levels of VDBP and 25(OH) vitamin D in type 2 diabetes.
authors.affiliation: Department of Pediatrics, Louisiana State University Health Sciences Center, Shreveport, LA, 71130, USA.
authors.forename: Sushil K
authors.initials: SK
authors.lastname: Jain
authors.affiliation: Department of Pediatrics, Louisiana State University Health Sciences Center, Shreveport, LA, 71130, USA.
authors.forename: Preeti
authors.initials: P
authors.lastname: Kanikarla-Marie
authors.affiliation: Department of Pediatrics, Louisiana State University Health Sciences Center, Shreveport, LA, 71130, USA.
authors.forename: Cassandra
authors.initials: C
authors.lastname: Warden
authors.affiliation: Department of Pediatrics, Louisiana State University Health Sciences Center, Shreveport, LA, 71130, USA.
authors.forename: David
authors.initials: D
authors.lastname: Micinski
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D002460:Cell Line; D003470:Culture Media / Q000737:chemistry; D003545:Cysteine / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental; D019587:Dietary Supplements; D005786:Gene Expression Regulation; D005947:Glucose / Q000032:analysis; D005721:Glutamate-Cysteine Ligase / Q000235:genetics / Q000378:metabolism; D005978:Glutathione / Q000097:blood* / Q000172:deficiency; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D011924:Rats, Zucker; D015854:Up-Regulation; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000097:blood; D014809:Vitamin D-Binding Protein / Q000097:blood* / Q000235:genetics
chemical_list: D015415:Biomarkers; D003470:Culture Media; D014809:Vitamin D-Binding Protein; D014807:Vitamin D; C104450:25-hydroxyvitamin D; D005721:Glutamate-Cysteine Ligase; C544143:GCLC protein, rat; D005978:Glutathione; D005947:Glucose; D003545:Cysteine
keywords: CYP2R1, D; GSH; Hepatocytes; L-cysteine; Type 2 diabetes; VDBP; Vitamin