title: Valproic Acid Improves Glucose Homeostasis by Increasing Beta-Cell Proliferation, Function, and Reducing its Apoptosis through HDAC Inhibition in Juvenile Diabetic Rat.
abstract: Recent evidence highlighted that there is a link between type-1 diabetes mellitus and histone deacetylases (HDACs) due to their involvement in beta-cell differentiation, proliferation, and function. The present study aimed to investigate the protective role of valproic acid (VPA) on beta-cell proliferation, function, and apoptosis in juvenile diabetic rat. Diabetes was induced in juvenile Sprague-Dawley rats by streptozotocin (75 mg/kg, i.p.) and VPA was administered at the doses of 150 and 300 mg/kg/day for 3 weeks by oral route. Various biochemical parameters, cellular alterations, and protein expression as well as apoptosis were assessed using different assays. VPA treatment significantly decreased plasma glucose, beta-cell damage, and apoptosis as well as increased the beta-cell function, insulin level/expression. The present study demonstrated that VPA improves beta-cell proliferation and function as well as reduces beta-cell apoptosis through HDAC inhibition. Our findings provide evidence that VPA may be useful for the treatment of juvenile diabetes.
authors.affiliation: Facility for Risk Assessment and Intervention Studies, Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, S.A.S. Nagar, Punjab, 160062, India. gbjena@gmail.com.
authors.forename: Sabbir
authors.initials: S
authors.lastname: Khan
authors.affiliation: Facility for Risk Assessment and Intervention Studies, Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, S.A.S. Nagar, Punjab, 160062, India. gbjena@niper.ac.in.
authors.forename: Gopabandhu
authors.initials: G
authors.lastname: Jena
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001786:Blood Glucose / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000401:mortality; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D005786:Gene Expression Regulation; D006442:Glycated Hemoglobin / Q000378:metabolism; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006655:Histone Deacetylases / Q000235:genetics* / Q000378:metabolism; D006657:Histones / Q000235:genetics / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000096:biosynthesis / Q000235:genetics; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013311:Streptozocin; D016019:Survival Analysis; D014635:Valproic Acid / Q000494:pharmacology*
chemical_list: D001786:Blood Glucose; D006442:Glycated Hemoglobin; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases; D006657:Histones; D007004:Hypoglycemic Agents; D007328:Insulin; D013311:Streptozocin; D014635:Valproic Acid
keywords: Apoptosis; Beta-Cell; Diabetes; HDAC inhibitor; Sodium Valproate