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このアイテムの引用には次の識別子を使用してください: http://hdl.handle.net/10564/3318

タイトル: Ipragliflozin, a sodium-glucose cotransporter 2 inhibitor, ameliorates the development of liver fibrosis in diabetic Otsuka Long-Evans Tokushima fatty rats.
その他のタイトル: SGLT2阻害薬であるイプラグリフロジンは2型糖尿病自然発症モデルであるOLETFラットにおいて肝線維化進展を抑制する。
著者: Nishimura, Norihisa
Kitade, Mitsuteru
Noguchi, Ryuichi
Namisaki, Tadashi
Moriya, Kei
Takeda, Kosuke
Okura, Yasushi
Aihara, Yosuke
Douhara, Akitoshi
Kawaratani, Hideto
Asada, Kiyoshi
Yoshiji, Hitoshi
キーワード: SGLT2 inhibitor
Liver fibrosis
Insulin resistance
発行日: 2016年12月
出版者: Springer
引用: Journal of gastroenterology Vol.51 No.12 p.1141-1149
抄録: BACKGROUND: It is widely understood that insulin resistance (IR) critically correlates with the development of liver fibrosis in several types of chronic liver injuries. Several experiments have proved that anti-IR treatment can alleviate liver fibrosis. Sodium-glucose cotransporter 2 (SGLT2) inhibitors comprise a new class of antidiabetic agents that inhibit glucose reabsorption in the renal proximal tubules, improving IR. The aim of this study was to elucidate the effect of an SGLT2 inhibitor on the development of liver fibrosis using obese diabetic Otsuka Long-Evans Tokushima fatty (OLETF) rats and their littermate nondiabetic Long-Evans Tokushima Otsuka (LETO) rats. METHODS: Male OLETF and LETO rats were intraperitoneally injected with porcine serum twice a week for 12 weeks to augment liver fibrogenesis. Different concentrations of ipragliflozin (3 and 6 mg/kg) were orally administered during the experimental period. Serological and histological data were examined at the end of the experimental period. The direct effect of ipragliflozin on the proliferation of a human hepatic stellate cell (HSC) line, LX-2, was also evaluated in vitro. RESULTS: OLETF rats, but not LETO rats, received 12 weeks of porcine serum injection to induce severe fibrosis. Treatment with ipragliflozin markedly attenuated the development of liver fibrosis and expression of hepatic fibrosis markers, such as alpha smooth muscle actin, collagen 1A1, and transforming growth factor beta (TGF-β), and improved IR in a dose-dependent manner in OLETF rats. In contrast, the proliferation of LX-2 in vitro was not affected, suggesting that ipragliflozin had no significant direct effect on the proliferation of HSCs. CONCLUSION: In conclusion, our dataset suggests that an SGLT2 inhibitor could alleviate the development of liver fibrosis by improving IR in naturally diabetic rats. This may provide the basis for creating new therapeutic strategies for chronic liver injuries with IR.
内容記述: 博士(医学)・甲第665号・平成29年3月15日
© Japanese Society of Gastroenterology 2016
The final publication is available at Springer via http://dx.doi.org/10.1007/s00535-016-1200-6.
URI: http://hdl.handle.net/10564/3318
ISSN: 09441174
学位授与番号: 24601A665
学位授与年月日: 2017-03-15
学位名: 博士(医学)
学位授与機関: 奈良県立医科大学


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