Effects of GLP-1RA and SGLT2i, Alone or in Combination, on Mouse Models of Type 2 Diabetes Representing Different Disease Stages

Glucagon-like peptide-1 receptor agonist (GLP-1RA) and sodium-dependent glucose transporter 2 inhibitor (SGLT2i), in addition to lowering glucose, have pleiotropic effects on the heart, kidneys, and liver. These drugs have thus come into widespread use for treating type 2 diabetes (T2DM). However, m...

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Autores principales:	Masao Koike, Hitoki Saito, Genta Kohno, Masahiro Takubo, Kentaro Watanabe, Hisamitsu Ishihara
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	type 2 diabetes mellitus GLP-1 receptor agonists SGLT2 inhibitors pancreatic β-cells fatty liver Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/1f053b864c004e1dad5afc1c1c81b380
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spelling	oai:doaj.org-article:1f053b864c004e1dad5afc1c1c81b3802021-11-11T16:55:47ZEffects of GLP-1RA and SGLT2i, Alone or in Combination, on Mouse Models of Type 2 Diabetes Representing Different Disease Stages10.3390/ijms2221114631422-00671661-6596https://doaj.org/article/1f053b864c004e1dad5afc1c1c81b3802021-10-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/11463https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Glucagon-like peptide-1 receptor agonist (GLP-1RA) and sodium-dependent glucose transporter 2 inhibitor (SGLT2i), in addition to lowering glucose, have pleiotropic effects on the heart, kidneys, and liver. These drugs have thus come into widespread use for treating type 2 diabetes (T2DM). However, mechanistic comparisons and effects of combining these drugs have not been adequately studied. Employing diet-induced obese (DIO) mice and db/db mice as models of the early and advanced stages of T2DM, we evaluated effects of single or combined use of liraglutide (a GLP-1RA) and ipragliflozin (a SGLT2i). Treatments with liraglutide and/or ipragliflozin for 28 days improved glycemic control and reduced hepatic lipid accumulation similarly in DIO mice. In contrast, in db/db mice, despite similar favorable effects on fatty liver, liraglutide exerted no beneficial effects on glycemic control. Improved glycemic control in db/db mice treated with ipragliflozin was accompanied by increased pancreatic β-cell area and insulin content, both of which tended to rise further when ipragliflozin was combined with liraglutide. Our data suggest that liraglutide is more efficient at an earlier stage and ipragliflozin can be effective in both stages. In addition, their combined use is a potential option for treating advanced stage diabetes with fatty liver disease.Masao KoikeHitoki SaitoGenta KohnoMasahiro TakuboKentaro WatanabeHisamitsu IshiharaMDPI AGarticletype 2 diabetes mellitusGLP-1 receptor agonistsSGLT2 inhibitorspancreatic β-cellsfatty liverBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 11463, p 11463 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	type 2 diabetes mellitus GLP-1 receptor agonists SGLT2 inhibitors pancreatic β-cells fatty liver Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	type 2 diabetes mellitus GLP-1 receptor agonists SGLT2 inhibitors pancreatic β-cells fatty liver Biology (General) QH301-705.5 Chemistry QD1-999 Masao Koike Hitoki Saito Genta Kohno Masahiro Takubo Kentaro Watanabe Hisamitsu Ishihara Effects of GLP-1RA and SGLT2i, Alone or in Combination, on Mouse Models of Type 2 Diabetes Representing Different Disease Stages
description	Glucagon-like peptide-1 receptor agonist (GLP-1RA) and sodium-dependent glucose transporter 2 inhibitor (SGLT2i), in addition to lowering glucose, have pleiotropic effects on the heart, kidneys, and liver. These drugs have thus come into widespread use for treating type 2 diabetes (T2DM). However, mechanistic comparisons and effects of combining these drugs have not been adequately studied. Employing diet-induced obese (DIO) mice and db/db mice as models of the early and advanced stages of T2DM, we evaluated effects of single or combined use of liraglutide (a GLP-1RA) and ipragliflozin (a SGLT2i). Treatments with liraglutide and/or ipragliflozin for 28 days improved glycemic control and reduced hepatic lipid accumulation similarly in DIO mice. In contrast, in db/db mice, despite similar favorable effects on fatty liver, liraglutide exerted no beneficial effects on glycemic control. Improved glycemic control in db/db mice treated with ipragliflozin was accompanied by increased pancreatic β-cell area and insulin content, both of which tended to rise further when ipragliflozin was combined with liraglutide. Our data suggest that liraglutide is more efficient at an earlier stage and ipragliflozin can be effective in both stages. In addition, their combined use is a potential option for treating advanced stage diabetes with fatty liver disease.
format	article
author	Masao Koike Hitoki Saito Genta Kohno Masahiro Takubo Kentaro Watanabe Hisamitsu Ishihara
author_facet	Masao Koike Hitoki Saito Genta Kohno Masahiro Takubo Kentaro Watanabe Hisamitsu Ishihara
author_sort	Masao Koike
title	Effects of GLP-1RA and SGLT2i, Alone or in Combination, on Mouse Models of Type 2 Diabetes Representing Different Disease Stages
title_short	Effects of GLP-1RA and SGLT2i, Alone or in Combination, on Mouse Models of Type 2 Diabetes Representing Different Disease Stages
title_full	Effects of GLP-1RA and SGLT2i, Alone or in Combination, on Mouse Models of Type 2 Diabetes Representing Different Disease Stages
title_fullStr	Effects of GLP-1RA and SGLT2i, Alone or in Combination, on Mouse Models of Type 2 Diabetes Representing Different Disease Stages
title_full_unstemmed	Effects of GLP-1RA and SGLT2i, Alone or in Combination, on Mouse Models of Type 2 Diabetes Representing Different Disease Stages
title_sort	effects of glp-1ra and sglt2i, alone or in combination, on mouse models of type 2 diabetes representing different disease stages
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/1f053b864c004e1dad5afc1c1c81b380
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Effects of GLP-1RA and SGLT2i, Alone or in Combination, on Mouse Models of Type 2 Diabetes Representing Different Disease Stages

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