Khan Sabbir, Jena Gopabandhu
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.
J Biochem Mol Toxicol. 2016 Sep;30(9):438-46. doi: 10.1002/jbt.21807. Epub 2016 Apr 15.
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.
最近的证据表明，1型糖尿病与组蛋白去乙酰化酶（HDACs）之间存在联系，因为它们参与β细胞的分化、增殖和功能。本研究旨在探讨丙戊酸（VPA）对幼年糖尿病大鼠β细胞增殖、功能和凋亡的保护作用。通过链脲佐菌素（75mg/kg，腹腔注射）诱导幼年Sprague-Dawley大鼠患糖尿病，并通过口服途径以150和300mg/kg/天的剂量给予VPA，持续3周。使用不同的检测方法评估各种生化参数、细胞变化、蛋白质表达以及凋亡情况。VPA治疗显著降低了血糖、β细胞损伤和凋亡，同时提高了β细胞功能、胰岛素水平/表达。本研究表明，VPA通过抑制HDAC改善β细胞增殖和功能，并减少β细胞凋亡。我们的研究结果提供了证据，表明VPA可能对治疗幼年糖尿病有用。
