The Selective SGLT2 Inhibitor Ipragliflozin Has a Therapeutic Effect on Nonalcoholic Steatohepatitis in Mice.
The Selective SGLT2 Inhibitor Ipragliflozin Has a Therapeutic Effect on Nonalcoholic Steatohepatitis in Mice.
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DOI：
10.1371/journal.pone.0146337
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Nakajima A
中科院分区：
文献类型：
--
作者：
Honda Y;Imajo K;Kato T;Kessoku T;Ogawa Y;Tomeno W;Kato S;Mawatari H;Fujita K;Yoneda M;Saito S;Nakajima A
近年来，非酒精性脂肪性肝炎（NASH）已成为全球范围内相当大的医疗负担。NASH的发病机制与2型糖尿病（T2 DM）和胰岛素抵抗有关。然而，缺乏治疗NASH的特异性药物。我们研究了选择性钠葡萄糖协同转运蛋白2抑制剂（SGLT 2 I）伊格列净对小鼠NASH的影响。我们使用胰淀素肝脏NASH模型（AMLN），其是导致肥胖和T2 DM的饮食诱导的NASH模型。给AMLN小鼠喂食AMLN饮食20周。SGLT 2 I小鼠喂食AMLN饲料12周，并喂食含40 mg伊格列净/kg的AMLN饲料8周。AMLN小鼠表现出肝脏脂肪变性、炎症和纤维化以及肥胖和胰岛素抵抗，这些特征在人类NASH中被识别。Ipraglivaline改善胰岛素抵抗和肝损伤。Ipraglivaline降低血清游离脂肪酸水平、肝脂质含量、凋亡细胞数量和纤维化面积;它还增加了肝脏的脂质流出。Ipraglivaline通过降低NASH模型小鼠的胰岛素抵抗和脂毒性来改善NASH的发病机制。我们的研究结果表明，伊格列净对NASH合并T2 DM有治疗作用。
In recent years, nonalcoholic steatohepatitis (NASH) has become a considerable healthcare burden worldwide. Pathogenesis of NASH is associated with type 2 diabetes mellitus (T2DM) and insulin resistance. However, a specific drug to treat NASH is lacking. We investigated the effect of the selective sodium glucose cotransporter 2 inhibitor (SGLT2I) ipragliflozin on NASH in mice. We used the Amylin liver NASH model (AMLN), which is a diet-induced model of NASH that results in obesity and T2DM. AMLN mice were fed an AMLN diet for 20 weeks. SGLT2I mice were fed an AMLN diet for 12 weeks and an AMLN diet with 40 mg ipragliflozin/kg for 8 weeks. AMLN mice showed steatosis, inflammation, and fibrosis in the liver as well as obesity and insulin resistance, features that are recognized in human NASH. Ipragliflozin improved insulin resistance and liver injury. Ipragliflozin decreased serum levels of free fatty acids, hepatic lipid content, the number of apoptotic cells, and areas of fibrosis; it also increased lipid outflow from the liver. Ipragliflozin improved the pathogenesis of NASH by reducing insulin resistance and lipotoxicity in NASH-model mice. Our results suggest that ipragliflozin has a therapeutic effect on NASH with T2DM.