DSpace About DSpace Software 日本語

01 奈良県立医科大学 >
012 大学院 >
0122 学位請求論文 >
01221 博士論文(医学) >
2016年度 >

Please use this identifier to cite or link to this item: http://hdl.handle.net/10564/3318

Title: Ipragliflozin, a sodium-glucose cotransporter 2 inhibitor, ameliorates the development of liver fibrosis in diabetic Otsuka Long-Evans Tokushima fatty rats.
Other Titles: 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。
Authors: Nishimura, Norihisa
Kitade, Mitsuteru
Noguchi, Ryuichi
Namisaki, Tadashi
Moriya, Kei
Takeda, Kosuke
Okura, Yasushi
Aihara, Yosuke
Douhara, Akitoshi
Kawaratani, Hideto
Asada, Kiyoshi
Yoshiji, Hitoshi
Keywords: SGLT2 inhibitor
Liver fibrosis
Insulin resistance
Issue Date: Dec-2016
Publisher: Springer
Citation: Journal of gastroenterology Vol.51 No.12 p.1141-1149 (2016 Dec)
Abstract: 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.
Description: 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
Academic Degrees and number: 24601A665
Degree-granting date: 2017-03-15
Degree name: 博士(医学)
Degree-granting institutions: 奈良県立医科大学
Appears in Collections:2016年度

Files in This Item:

File Description SizeFormat
01_甲664本文の要旨.pdf甲665本文の要旨266.44 kBAdobe PDFView/Open
02_甲665審査要旨.pdf甲665審査要旨599.35 kBAdobe PDFView/Open
03甲665本文.pdf03甲665本文5.51 MBAdobe PDFView/Open

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.


Valid XHTML 1.0! DSpace Software Copyright © 2002-2010  Duraspace - Feedback