Early combination therapy of empagliflozin and linagliptin exerts beneficial effects on pancreatic β cells in diabetic db/db mice

Abstract Effects of combination therapy of dipeptidyl peptidase-4 (DPP-4) inhibitor and sodium-glucose co-transporter 2 (SGLT2) inhibitor on β-cells are still unclear, although combination agent of these two drugs has become common in clinical practice. Therefore, we aimed to elucidate the effects o...

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Autores principales:	Yoshiro Fushimi, Atsushi Obata, Junpei Sanada, Yuka Nogami, Tomoko Ikeda, Yuki Yamasaki, Yoshiyuki Obata, Masashi Shimoda, Shuhei Nakanishi, Tomoatsu Mune, Kohei Kaku, Hideaki Kaneto
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/3dd05362d0c04b16bbd3922fdc75d61f
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spelling	oai:doaj.org-article:3dd05362d0c04b16bbd3922fdc75d61f2021-12-02T15:08:39ZEarly combination therapy of empagliflozin and linagliptin exerts beneficial effects on pancreatic β cells in diabetic db/db mice10.1038/s41598-021-94896-w2045-2322https://doaj.org/article/3dd05362d0c04b16bbd3922fdc75d61f2021-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-94896-whttps://doaj.org/toc/2045-2322Abstract Effects of combination therapy of dipeptidyl peptidase-4 (DPP-4) inhibitor and sodium-glucose co-transporter 2 (SGLT2) inhibitor on β-cells are still unclear, although combination agent of these two drugs has become common in clinical practice. Therefore, we aimed to elucidate the effects of DPP-4 inhibitor and/or SGLT2 inhibitor on β-cell mass and function and compared their effects between in an early and advanced phase of diabetes. We used 7-week-old db/db mice as an early phase and 16-week-old mice as an advanced phase and treated them for 2 weeks with oral administration of linagliptin, empagliflozin, linagliptin + empagliflozin (L + E group), and 0.5% carboxymethylcellulose (Cont group). Blood glucose levels in Empa and L + E group were significantly lower than Cont group after treatment. In addition, β-cell mass in L + E group was significantly larger than Cont group only in an early phase, accompanied by increased Ki67-positive β-cell ratio. In isolated islets, mRNA expression levels of insulin and its transcription factors were all significantly higher only in L + E group in an early phase. Furthermore, mRNA expression levels related to β-cell differentiation and proliferation were significantly increased only in L + E group in an early phase. In conclusion, combination of DPP-4 inhibitor and SGLT2 inhibitor exerts more beneficial effects on β-cell mass and function, especially in an early phase of diabetes rather than an advanced phase.Yoshiro FushimiAtsushi ObataJunpei SanadaYuka NogamiTomoko IkedaYuki YamasakiYoshiyuki ObataMasashi ShimodaShuhei NakanishiTomoatsu MuneKohei KakuHideaki KanetoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yoshiro Fushimi Atsushi Obata Junpei Sanada Yuka Nogami Tomoko Ikeda Yuki Yamasaki Yoshiyuki Obata Masashi Shimoda Shuhei Nakanishi Tomoatsu Mune Kohei Kaku Hideaki Kaneto Early combination therapy of empagliflozin and linagliptin exerts beneficial effects on pancreatic β cells in diabetic db/db mice
description	Abstract Effects of combination therapy of dipeptidyl peptidase-4 (DPP-4) inhibitor and sodium-glucose co-transporter 2 (SGLT2) inhibitor on β-cells are still unclear, although combination agent of these two drugs has become common in clinical practice. Therefore, we aimed to elucidate the effects of DPP-4 inhibitor and/or SGLT2 inhibitor on β-cell mass and function and compared their effects between in an early and advanced phase of diabetes. We used 7-week-old db/db mice as an early phase and 16-week-old mice as an advanced phase and treated them for 2 weeks with oral administration of linagliptin, empagliflozin, linagliptin + empagliflozin (L + E group), and 0.5% carboxymethylcellulose (Cont group). Blood glucose levels in Empa and L + E group were significantly lower than Cont group after treatment. In addition, β-cell mass in L + E group was significantly larger than Cont group only in an early phase, accompanied by increased Ki67-positive β-cell ratio. In isolated islets, mRNA expression levels of insulin and its transcription factors were all significantly higher only in L + E group in an early phase. Furthermore, mRNA expression levels related to β-cell differentiation and proliferation were significantly increased only in L + E group in an early phase. In conclusion, combination of DPP-4 inhibitor and SGLT2 inhibitor exerts more beneficial effects on β-cell mass and function, especially in an early phase of diabetes rather than an advanced phase.
format	article
author	Yoshiro Fushimi Atsushi Obata Junpei Sanada Yuka Nogami Tomoko Ikeda Yuki Yamasaki Yoshiyuki Obata Masashi Shimoda Shuhei Nakanishi Tomoatsu Mune Kohei Kaku Hideaki Kaneto
author_facet	Yoshiro Fushimi Atsushi Obata Junpei Sanada Yuka Nogami Tomoko Ikeda Yuki Yamasaki Yoshiyuki Obata Masashi Shimoda Shuhei Nakanishi Tomoatsu Mune Kohei Kaku Hideaki Kaneto
author_sort	Yoshiro Fushimi
title	Early combination therapy of empagliflozin and linagliptin exerts beneficial effects on pancreatic β cells in diabetic db/db mice
title_short	Early combination therapy of empagliflozin and linagliptin exerts beneficial effects on pancreatic β cells in diabetic db/db mice
title_full	Early combination therapy of empagliflozin and linagliptin exerts beneficial effects on pancreatic β cells in diabetic db/db mice
title_fullStr	Early combination therapy of empagliflozin and linagliptin exerts beneficial effects on pancreatic β cells in diabetic db/db mice
title_full_unstemmed	Early combination therapy of empagliflozin and linagliptin exerts beneficial effects on pancreatic β cells in diabetic db/db mice
title_sort	early combination therapy of empagliflozin and linagliptin exerts beneficial effects on pancreatic β cells in diabetic db/db mice
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/3dd05362d0c04b16bbd3922fdc75d61f
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Early combination therapy of empagliflozin and linagliptin exerts beneficial effects on pancreatic β cells in diabetic db/db mice

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