title: Vitamin K1 alleviates streptozotocin-induced type 1 diabetes by mitigating free radical stress, as well as inhibiting NF-κB activation and iNOS expression in rat pancreas.
abstract: OBJECTIVE
  The aim of this study was to understand the mechanism of action of vitamin K1 against streptozotocin (STZ)-induced diabetes.
  
  
  METHODS
  Male Wistar rats were administered 35 mg/kg STZ and after 3 d were treated with vitamin K1 (5 mg/kg, twice a week) for 3 months. Blood glucose was monitored twice a month. At the end of the study, animals were sacrificed and pancreas dissected out and analyzed for free radicals, antioxidants, metabolic enzymes related to glucose, membrane ATPases, histopathological evaluation, and expression of nuclear factor (NF)-κB and inducible nitric oxide synthase (iNOS). Glycated hemoglobin, plasma insulin, and islet area were determined at the end of the study.
  
  
  RESULTS
  Treatment of STZ-induced type 1 diabetic rats with vitamin K1 reduced oxidative stress, enhanced antioxidants, and inhibited aldose reductase in pancreas. Vitamin K1 administration rescued endocrine pancreas from STZ-induced cell death, resulting in enhanced insulin secretion and normal blood glucose and glycosylated hemoglobin levels. Histologic analyses also showed the antidiabetic potential of vitamin K1. Measure of pancreatic islet area showed an increase in the islet area upon vitamin K1 treatment when compared with the STZ-administered group, suggesting the possibility of regeneration. To understand the mechanism involved in vitamin K1 mediated changes, we performed immunohistochemical analyses for NF-κB and iNOS enzyme. Vitamin K1 was shown to suppress NF-κB activation and iNOS expression in the islets upon administration of STZ.
  
  
  CONCLUSIONS
  This work shows, to our knowledge for the first time, the mechanism of action of vitamin K1 against type 1 diabetes and the possible therapeutic use of this vitamin in stimulating islet cell proliferation/regeneration.
authors.affiliation: Department of Bioengineering, School of Chemical & Biotechnology, SASTRA University, Thanjavur, India.
authors.forename: M K N Sai
authors.initials: MK
authors.lastname: Varsha
authors.affiliation: Department of Bioengineering, School of Chemical & Biotechnology, SASTRA University, Thanjavur, India. Electronic address: raman@biotech.sastra.edu.
authors.forename: R
authors.initials: R
authors.lastname: Thiagarajan
authors.affiliation: Department of Zoology, University of Madras, Guindy Campus, Chennai, India.
authors.forename: R
authors.initials: R
authors.lastname: Manikandan
authors.affiliation: Department of Zoology, University of Madras, Guindy Campus, Chennai, India.
authors.forename: G
authors.initials: G
authors.lastname: Dhanasekaran
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000188:drug therapy*; D003922:Diabetes Mellitus, Type 1 / Q000139:chemically induced / Q000188:drug therapy; D004305:Dose-Response Relationship, Drug; D006454:Hemoglobins / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007328:Insulin / Q000097:blood / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008297:Male; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors* / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013311:Streptozocin / Q000009:adverse effects; D010837:Vitamin K 1 / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D001786:Blood Glucose; D006454:Hemoglobins; D007004:Hypoglycemic Agents; D007328:Insulin; D016328:NF-kappa B; D013311:Streptozocin; D010837:Vitamin K 1; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat
keywords: Aldose reductase; Antioxidant; Diabetes; Oxidative stress; Pancreas; Type 1 diabetes; Vitamin K