Facility for Risk Assessment and Intervention Studies, Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, Sector-67, S.A.S. Nagar, Punjab 160062, India.
Chem Biol Interact. 2014 Apr 25;213:1-12. doi: 10.1016/j.cbi.2014.02.001. Epub 2014 Feb 11.
Type 1 diabetes (T1D) also known as juvenile diabetes is a chronic autoimmune disorder that precipitates in genetically susceptible individuals by environmental factors particularly during early age. Both genetic and epigenetic factors are implicated in the beta-cell development, proliferation, differentiation and function. Recent evidences suggested that there is a link between diabetes and histone deacetylases (HDACs), because HDAC inhibitors promote beta-cell development, proliferation and function as well as improve glucose homeostasis. Sodium butyrate (NaB) is a short chain fatty acid having HDAC inhibition activity. The present study was aimed to investigate the protective role of NaB treatment on the beta-cell proliferation, function and glucose homeostasis as well as apoptosis in juvenile diabetic rat. Diabetes was induced by single injection of STZ (60 mg/kg, i.p.) in chilled citrate buffer, while NaB (500 mg/kg/day) was administrated by i.p. route for 21 days as pre- and post-treatment schedule. Plasma glucose and insulin levels, HbA1c, glucose tolerance, apoptosis, and expression of proliferating cell nuclear antigen (PCNA), p38, p53, caspase-3, extracellular signal-regulated kinase-1/2 (ERK-1/2), forkhead box protein O1 (FOXO1) and insulin receptor substrate-1 (IRS-1) as well as histone acetylation were evaluated. NaB treatment decreased plasma glucose, HbA1c, beta-cell apoptosis and improved plasma insulin level and glucose homeostasis through HDAC inhibition and histone acetylation in diabetic animal as compared to control. NaB treatment improved the beta-cell proliferation, function and glucose homeostasis as well as reduced beta-cell apoptosis in juvenile diabetic rat by the modulation of p38/ERK MAPK and apoptotic pathway.
1 型糖尿病（T1D）也称为青少年糖尿病，是一种慢性自身免疫性疾病，在遗传易感个体中由环境因素特别是在早期诱发。遗传和表观遗传因素都与β细胞的发育、增殖、分化和功能有关。最近的证据表明，糖尿病与组蛋白去乙酰化酶（HDACs）之间存在联系，因为 HDAC 抑制剂可促进β细胞的发育、增殖和功能，改善葡萄糖稳态。丁酸钠（NaB）是一种具有 HDAC 抑制活性的短链脂肪酸。本研究旨在探讨 NaB 治疗对幼年糖尿病大鼠β细胞增殖、功能和葡萄糖稳态以及细胞凋亡的保护作用。糖尿病通过 STZ（60mg/kg，ip）在冰冷的柠檬酸盐缓冲液中单次注射诱导，而 NaB（500mg/kg/天）通过 ip 途径在 21 天内进行预处理和后处理。评估血浆葡萄糖和胰岛素水平、HbA1c、葡萄糖耐量、细胞凋亡以及增殖细胞核抗原（PCNA）、p38、p53、caspase-3、细胞外信号调节激酶-1/2（ERK-1/2）、叉头框蛋白 O1（FOXO1）和胰岛素受体底物-1（IRS-1）的表达以及组蛋白乙酰化。与对照组相比，NaB 治疗通过抑制 HDAC 和组蛋白乙酰化降低了糖尿病动物的血浆葡萄糖、HbA1c、β细胞凋亡，并改善了血浆胰岛素水平和葡萄糖稳态。NaB 治疗通过调节 p38/ERK MAPK 和凋亡途径改善了幼年糖尿病大鼠的β细胞增殖、功能和葡萄糖稳态，并减少了β细胞凋亡。
