Treatment with the SGLT2 inhibitor luseogliflozin improves nonalcoholic steatohepatitis in a rodent model with diabetes mellitus.
Treatment with the SGLT2 inhibitor luseogliflozin improves nonalcoholic steatohepatitis in a rodent model with diabetes mellitus.
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DOI：
10.1186/s13098-015-0102-8
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发表时间：
2015
影响因子：
4.8
通讯作者：
Asano T
中科院分区：
文献类型：
--
作者：
Qiang S;Nakatsu Y;Seno Y;Fujishiro M;Sakoda H;Kushiyama A;Mori K;Matsunaga Y;Yamamotoya T;Kamata H;Asano T
胰岛素抵抗伴血糖升高是非酒精性脂肪性肝炎（NASH）的危险因素。我们使用啮齿动物模型研究了钠葡萄糖协同转运蛋白2（SGLT 2）抑制剂鲁赛格列汀对NASH发展的影响。用烟酰胺和链脲佐菌素（NA/STZ）处理小鼠以降低胰岛素分泌能力，然后喂食含有反式脂肪酸（HFDT）的高脂肪饮食8周。在此期间，将NA/STZ HFDT喂养的小鼠分为两组，用鲁司格列汀处理或未处理。在NA/STZ治疗和HFDT喂养的小鼠中的葡萄糖升高通过鲁塞格列汀给药显著改善。虽然HFDT喂养诱导NASH发展，如肝脏重量增加伴脂质蓄积和血清丙氨酸氨基转移酶升高所示，但这些变化在鲁索格列汀治疗组中均减弱。此外，纤维化变化和胶原沉积增加，胶原蛋白1和平滑肌肌动蛋白和炎性细胞因子表达的上调，观察到在HFDT喂养的小鼠肝脏也正常化鲁赛格列净管理。总之，在小鼠中获得的这些结果证明了给予SGLT 2抑制剂治疗糖尿病相关NASH的有利作用。我们预计这些药物将适用于人类。
Insulin resistance with elevated glucose is a risk factor for non-alcoholic steatohepatitis (NASH). We investigated the effects of the sodium glucose cotransporter 2 (SGLT2) inhibitor luseogliflozin on NASH development using a rodent model. Mice were treated with both nicotinamide and streptozotocin (NA/STZ) to reduce insulin secretory capacity, and then fed a high fat diet containing trans fatty acids (HFDT) for 8 weeks. The NA/STZ HFDT-fed mice were divided into two groups, either treated with luseogliflozin or untreated, during this period. The glucose elevations in the NA/STZ-treated and HFDT-fed mice were significantly improved by luseogliflozin administration. While HFDT feeding induced NASH development as shown by liver weight gain with lipid accumulation and increased serum alanine aminotransferase, these changes were all attenuated in the group treated with luseogliflozin. In addition, fibrotic change and increases in collagen deposition with upregulations of collagen1 and smooth muscle actin and inflammatory cytokine expressions observed in the HFDT-fed mouse livers were also normalized by luseogliflozin administration. Taken together, these results obtained in mice demonstrate the favorable effects of administering SGLT2 inhibitors, for the treatment of NASH associated with diabetes mellitus. We anticipate that these agents would be applicable to humans.