Metabolic recovery of lipodystrophy, liver steatosis, and pancreatic β cell proliferation after the withdrawal of OSI-906

Abstract Growth factor signaling via insulin receptor (IR) and IGF-1 receptor (IGF1R) plays several important roles in the pathogenesis of metabolic syndrome and diabetes. OSI-906 (linsitinib), an anti-tumor drug, is an orally bioavailable dual inhibitor of IR and IGF1R. To investigate the recovery...

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Autores principales:	Kazuki Tajima, Jun Shirakawa, Yu Togashi, Shunsuke Yamazaki, Tomoko Okuyama, Mayu Kyohara, Hiromi Konishi, Yasuo Terauchi
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/09a9086494a640ca8284695f8b491659
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spelling	oai:doaj.org-article:09a9086494a640ca8284695f8b4916592021-12-02T11:50:57ZMetabolic recovery of lipodystrophy, liver steatosis, and pancreatic β cell proliferation after the withdrawal of OSI-90610.1038/s41598-017-04304-52045-2322https://doaj.org/article/09a9086494a640ca8284695f8b4916592017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-04304-5https://doaj.org/toc/2045-2322Abstract Growth factor signaling via insulin receptor (IR) and IGF-1 receptor (IGF1R) plays several important roles in the pathogenesis of metabolic syndrome and diabetes. OSI-906 (linsitinib), an anti-tumor drug, is an orally bioavailable dual inhibitor of IR and IGF1R. To investigate the recovery from metabolic changes induced by the acute inhibition of IR and IGF1R in adult mice, mice were treated with OSI-906 or a vehicle for 7 days and the results were analyzed on the last day of injection (Day 7) or after 7 or 21 days of withdrawal (Day 14 or Day 28). On day 7, the visceral white fat mass was significantly reduced in mice treated with OSI-906 accompanied by a reduced expression of leptin and an increased expression of the lipolysis-related genes Lpl and Atgl. Interestingly, the lipoatrophy and the observed changes in gene expression were completely reversed on day 14. Similarly, liver steatosis and β cell proliferation were transiently observed on day 7 but had disappeared by day 14. Taken together, these results suggest that this model for the acute inhibition of systemic IR/IGF1R signaling may be useful for investigating the recovery from metabolic disorders induced by impaired growth factor signaling.Kazuki TajimaJun ShirakawaYu TogashiShunsuke YamazakiTomoko OkuyamaMayu KyoharaHiromi KonishiYasuo TerauchiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-14 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Kazuki Tajima Jun Shirakawa Yu Togashi Shunsuke Yamazaki Tomoko Okuyama Mayu Kyohara Hiromi Konishi Yasuo Terauchi Metabolic recovery of lipodystrophy, liver steatosis, and pancreatic β cell proliferation after the withdrawal of OSI-906
description	Abstract Growth factor signaling via insulin receptor (IR) and IGF-1 receptor (IGF1R) plays several important roles in the pathogenesis of metabolic syndrome and diabetes. OSI-906 (linsitinib), an anti-tumor drug, is an orally bioavailable dual inhibitor of IR and IGF1R. To investigate the recovery from metabolic changes induced by the acute inhibition of IR and IGF1R in adult mice, mice were treated with OSI-906 or a vehicle for 7 days and the results were analyzed on the last day of injection (Day 7) or after 7 or 21 days of withdrawal (Day 14 or Day 28). On day 7, the visceral white fat mass was significantly reduced in mice treated with OSI-906 accompanied by a reduced expression of leptin and an increased expression of the lipolysis-related genes Lpl and Atgl. Interestingly, the lipoatrophy and the observed changes in gene expression were completely reversed on day 14. Similarly, liver steatosis and β cell proliferation were transiently observed on day 7 but had disappeared by day 14. Taken together, these results suggest that this model for the acute inhibition of systemic IR/IGF1R signaling may be useful for investigating the recovery from metabolic disorders induced by impaired growth factor signaling.
format	article
author	Kazuki Tajima Jun Shirakawa Yu Togashi Shunsuke Yamazaki Tomoko Okuyama Mayu Kyohara Hiromi Konishi Yasuo Terauchi
author_facet	Kazuki Tajima Jun Shirakawa Yu Togashi Shunsuke Yamazaki Tomoko Okuyama Mayu Kyohara Hiromi Konishi Yasuo Terauchi
author_sort	Kazuki Tajima
title	Metabolic recovery of lipodystrophy, liver steatosis, and pancreatic β cell proliferation after the withdrawal of OSI-906
title_short	Metabolic recovery of lipodystrophy, liver steatosis, and pancreatic β cell proliferation after the withdrawal of OSI-906
title_full	Metabolic recovery of lipodystrophy, liver steatosis, and pancreatic β cell proliferation after the withdrawal of OSI-906
title_fullStr	Metabolic recovery of lipodystrophy, liver steatosis, and pancreatic β cell proliferation after the withdrawal of OSI-906
title_full_unstemmed	Metabolic recovery of lipodystrophy, liver steatosis, and pancreatic β cell proliferation after the withdrawal of OSI-906
title_sort	metabolic recovery of lipodystrophy, liver steatosis, and pancreatic β cell proliferation after the withdrawal of osi-906
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/09a9086494a640ca8284695f8b491659
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Metabolic recovery of lipodystrophy, liver steatosis, and pancreatic β cell proliferation after the withdrawal of OSI-906

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