Sodium butyrate reduces insulin-resistance, fat accumulation and dyslipidemia in type-2 diabetic rat: A comparative study with metformin
Sodium butyrate reduces insulin-resistance, fat accumulation and dyslipidemia in type-2 diabetic rat: A comparative study with metformin
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DOI：
10.1016/j.cbi.2016.06.007
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发表时间：
2016-07-25
影响因子：
5.1
通讯作者：
Jena, Gopabandhu
中科院分区：
文献类型：
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作者：
Khan, Sabbir;Jena, Gopabandhu
组蛋白去乙酰化酶（HDACs）可以使组蛋白、各种转录因子和调控蛋白去乙酰化，直接或间接影响糖代谢。本研究旨在比较丁酸钠（NaB）和二甲双胍对2型糖尿病大鼠血糖稳态、胰岛素抵抗、脂肪蓄积和血脂异常的影响。通过高脂饮食（HFD）和低剂量链脲佐菌素（STZ，35 mg/kg）的组合在Sprague-Dawley大鼠中形成糖尿病。分别通过腹膜内和经口途径给予200和400 mg/kg NaB每日两次以及二甲双胍（作为阳性对照）150 mg/kg每日两次，连续10周。NaB治疗显著降低了血糖、HbA 1c、胰岛素抵抗、血脂异常和新生血管生成，与二甲双胍治疗相当。此外，NaB处理改善了肝脏中的微泡和大泡脂肪变性和棕色脂肪组织、白色脂肪组织中的脂肪沉积（脂肪细胞肥大）以及胰腺β细胞损伤。在本研究中，NaB和二甲双胍均抑制糖尿病相关的HDAC活性增加，从而增加肝脏中组蛋白H3的乙酰化。目前的研究结果表明，NaB和二甲双胍降低胰岛素抵抗，血脂异常，脂肪堆积和脂肪生成，从而改善大鼠的葡萄糖稳态。因此，NaB可能是一个有前途的分子，用于预防和治疗2型糖尿病和血脂异常。(C)2016爱思唯尔爱尔兰有限公司版权所有。
Recent evidences highlighted that histone deacetylases (HDACs) can deacetylate the histone, various transcription factors and regulatory proteins, which directly or indirectly affect glucose metabolism. The present study aimed to evaluate the comparative effects of sodium butyrate (NaB) and metformin on the glucose homeostasis, insulin-resistance, fat accumulation and dyslipidemia in type-2 diabetic rat. Diabetes was developed in Sprague-Dawley rats by the combination of high-fat diet (HFD) and low dose streptozotocin (STZ, 35 mg/kg). NaB at the doses of 200 and 400 mg/kg twice daily as well as metformin (as a positive control) 150 mg/kg twice daily for 10 consecutive weeks were administered by i.p. and oral route, respectively. NaB treatment significantly reduced the plasma glucose, HbA1c, insulin-resistance, dyslipidemia and gluconeogenesis, which are comparable to metformin treatment. Further, NaB treatment ameliorated the micro-and macro-vesicular steatosis in liver and fat deposition in brown adipose tissue, white adipose tissue (adipocytes hypertrophy) as well as pancreatic beta-cell damage. In the present study, both NaB and metformin inhibited the diabetes-associated increased HDACs activity, thereby increased the acetylation of histone H3 in liver. The present findings demonstrated that NaB and metformin reduced insulin-resistance, dyslipidemia, fat accumulation and gluconeogenesis thereby improved the glucose homeostasis in rat. Thus, NaB might be a promising molecule for the prevention and treatment of type-2 diabetes and dyslipidemia. (C) 2016 Elsevier Ireland Ltd. All rights reserved.