Increased systemic glucose tolerance with increased muscle glucose uptake in transgenic mice overexpressing RXRγ in skeletal muscle.

<h4>Background</h4>Retinoid X receptor (RXR) γ is a nuclear receptor-type transcription factor expressed mostly in skeletal muscle, and regulated by nutritional conditions. Previously, we established transgenic mice overexpressing RXRγ in skeletal muscle (RXRγ mice), which showed lower b...

Descripción completa

Guardado en:
Detalles Bibliográficos
Autores principales: Satoshi Sugita, Yasutomi Kamei, Fumiko Akaike, Takayoshi Suganami, Sayaka Kanai, Maki Hattori, Yasuko Manabe, Nobuharu Fujii, Takako Takai-Igarashi, Miki Tadaishi, Jun-ichiro Oka, Hiroyuki Aburatani, Tetsuya Yamada, Hideki Katagiri, Saori Kakehi, Yoshifumi Tamura, Hideo Kubo, Kenichi Nishida, Shinji Miura, Osamu Ezaki, Yoshihiro Ogawa
Formato: article
Lenguaje:EN
Publicado: Public Library of Science (PLoS) 2011
Materias:
R
Q
Acceso en línea:https://doaj.org/article/f594ae68b5684d44a1cc71a637e8ace9
Etiquetas: Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
id oai:doaj.org-article:f594ae68b5684d44a1cc71a637e8ace9
record_format dspace
spelling oai:doaj.org-article:f594ae68b5684d44a1cc71a637e8ace92021-11-18T06:52:56ZIncreased systemic glucose tolerance with increased muscle glucose uptake in transgenic mice overexpressing RXRγ in skeletal muscle.1932-620310.1371/journal.pone.0020467https://doaj.org/article/f594ae68b5684d44a1cc71a637e8ace92011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21655215/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Retinoid X receptor (RXR) γ is a nuclear receptor-type transcription factor expressed mostly in skeletal muscle, and regulated by nutritional conditions. Previously, we established transgenic mice overexpressing RXRγ in skeletal muscle (RXRγ mice), which showed lower blood glucose than the control mice. Here we investigated their glucose metabolism.<h4>Methodology/principal findings</h4>RXRγ mice were subjected to glucose and insulin tolerance tests, and glucose transporter expression levels, hyperinsulinemic-euglycemic clamp and glucose uptake were analyzed. Microarray and bioinformatics analyses were done. The glucose tolerance test revealed higher glucose disposal in RXRγ mice than in control mice, but insulin tolerance test revealed no difference in the insulin-induced hypoglycemic response. In the hyperinsulinemic-euglycemic clamp study, the basal glucose disposal rate was higher in RXRγ mice than in control mice, indicating an insulin-independent increase in glucose uptake. There was no difference in the rate of glucose infusion needed to maintain euglycemia (glucose infusion rate) between the RXRγ and control mice, which is consistent with the result of the insulin tolerance test. Skeletal muscle from RXRγ mice showed increased Glut1 expression, with increased glucose uptake, in an insulin-independent manner. Moreover, we performed in vivo luciferase reporter analysis using Glut1 promoter (Glut1-Luc). Combination of RXRγ and PPARδ resulted in an increase in Glut1-Luc activity in skeletal muscle in vivo. Microarray data showed that RXRγ overexpression increased a diverse set of genes, including glucose metabolism genes, whose promoter contained putative PPAR-binding motifs.<h4>Conclusions/significance</h4>Systemic glucose metabolism was increased in transgenic mice overexpressing RXRγ. The enhanced glucose tolerance in RXRγ mice may be mediated at least in part by increased Glut1 in skeletal muscle. These results show the importance of skeletal muscle gene regulation in systemic glucose metabolism. Increasing RXRγ expression may be a novel therapeutic strategy against type 2 diabetes.Satoshi SugitaYasutomi KameiFumiko AkaikeTakayoshi SuganamiSayaka KanaiMaki HattoriYasuko ManabeNobuharu FujiiTakako Takai-IgarashiMiki TadaishiJun-ichiro OkaHiroyuki AburataniTetsuya YamadaHideki KatagiriSaori KakehiYoshifumi TamuraHideo KuboKenichi NishidaShinji MiuraOsamu EzakiYoshihiro OgawaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 5, p e20467 (2011)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Satoshi Sugita
Yasutomi Kamei
Fumiko Akaike
Takayoshi Suganami
Sayaka Kanai
Maki Hattori
Yasuko Manabe
Nobuharu Fujii
Takako Takai-Igarashi
Miki Tadaishi
Jun-ichiro Oka
Hiroyuki Aburatani
Tetsuya Yamada
Hideki Katagiri
Saori Kakehi
Yoshifumi Tamura
Hideo Kubo
Kenichi Nishida
Shinji Miura
Osamu Ezaki
Yoshihiro Ogawa
Increased systemic glucose tolerance with increased muscle glucose uptake in transgenic mice overexpressing RXRγ in skeletal muscle.
description <h4>Background</h4>Retinoid X receptor (RXR) γ is a nuclear receptor-type transcription factor expressed mostly in skeletal muscle, and regulated by nutritional conditions. Previously, we established transgenic mice overexpressing RXRγ in skeletal muscle (RXRγ mice), which showed lower blood glucose than the control mice. Here we investigated their glucose metabolism.<h4>Methodology/principal findings</h4>RXRγ mice were subjected to glucose and insulin tolerance tests, and glucose transporter expression levels, hyperinsulinemic-euglycemic clamp and glucose uptake were analyzed. Microarray and bioinformatics analyses were done. The glucose tolerance test revealed higher glucose disposal in RXRγ mice than in control mice, but insulin tolerance test revealed no difference in the insulin-induced hypoglycemic response. In the hyperinsulinemic-euglycemic clamp study, the basal glucose disposal rate was higher in RXRγ mice than in control mice, indicating an insulin-independent increase in glucose uptake. There was no difference in the rate of glucose infusion needed to maintain euglycemia (glucose infusion rate) between the RXRγ and control mice, which is consistent with the result of the insulin tolerance test. Skeletal muscle from RXRγ mice showed increased Glut1 expression, with increased glucose uptake, in an insulin-independent manner. Moreover, we performed in vivo luciferase reporter analysis using Glut1 promoter (Glut1-Luc). Combination of RXRγ and PPARδ resulted in an increase in Glut1-Luc activity in skeletal muscle in vivo. Microarray data showed that RXRγ overexpression increased a diverse set of genes, including glucose metabolism genes, whose promoter contained putative PPAR-binding motifs.<h4>Conclusions/significance</h4>Systemic glucose metabolism was increased in transgenic mice overexpressing RXRγ. The enhanced glucose tolerance in RXRγ mice may be mediated at least in part by increased Glut1 in skeletal muscle. These results show the importance of skeletal muscle gene regulation in systemic glucose metabolism. Increasing RXRγ expression may be a novel therapeutic strategy against type 2 diabetes.
format article
author Satoshi Sugita
Yasutomi Kamei
Fumiko Akaike
Takayoshi Suganami
Sayaka Kanai
Maki Hattori
Yasuko Manabe
Nobuharu Fujii
Takako Takai-Igarashi
Miki Tadaishi
Jun-ichiro Oka
Hiroyuki Aburatani
Tetsuya Yamada
Hideki Katagiri
Saori Kakehi
Yoshifumi Tamura
Hideo Kubo
Kenichi Nishida
Shinji Miura
Osamu Ezaki
Yoshihiro Ogawa
author_facet Satoshi Sugita
Yasutomi Kamei
Fumiko Akaike
Takayoshi Suganami
Sayaka Kanai
Maki Hattori
Yasuko Manabe
Nobuharu Fujii
Takako Takai-Igarashi
Miki Tadaishi
Jun-ichiro Oka
Hiroyuki Aburatani
Tetsuya Yamada
Hideki Katagiri
Saori Kakehi
Yoshifumi Tamura
Hideo Kubo
Kenichi Nishida
Shinji Miura
Osamu Ezaki
Yoshihiro Ogawa
author_sort Satoshi Sugita
title Increased systemic glucose tolerance with increased muscle glucose uptake in transgenic mice overexpressing RXRγ in skeletal muscle.
title_short Increased systemic glucose tolerance with increased muscle glucose uptake in transgenic mice overexpressing RXRγ in skeletal muscle.
title_full Increased systemic glucose tolerance with increased muscle glucose uptake in transgenic mice overexpressing RXRγ in skeletal muscle.
title_fullStr Increased systemic glucose tolerance with increased muscle glucose uptake in transgenic mice overexpressing RXRγ in skeletal muscle.
title_full_unstemmed Increased systemic glucose tolerance with increased muscle glucose uptake in transgenic mice overexpressing RXRγ in skeletal muscle.
title_sort increased systemic glucose tolerance with increased muscle glucose uptake in transgenic mice overexpressing rxrγ in skeletal muscle.
publisher Public Library of Science (PLoS)
publishDate 2011
url https://doaj.org/article/f594ae68b5684d44a1cc71a637e8ace9
work_keys_str_mv AT satoshisugita increasedsystemicglucosetolerancewithincreasedmuscleglucoseuptakeintransgenicmiceoverexpressingrxrginskeletalmuscle
AT yasutomikamei increasedsystemicglucosetolerancewithincreasedmuscleglucoseuptakeintransgenicmiceoverexpressingrxrginskeletalmuscle
AT fumikoakaike increasedsystemicglucosetolerancewithincreasedmuscleglucoseuptakeintransgenicmiceoverexpressingrxrginskeletalmuscle
AT takayoshisuganami increasedsystemicglucosetolerancewithincreasedmuscleglucoseuptakeintransgenicmiceoverexpressingrxrginskeletalmuscle
AT sayakakanai increasedsystemicglucosetolerancewithincreasedmuscleglucoseuptakeintransgenicmiceoverexpressingrxrginskeletalmuscle
AT makihattori increasedsystemicglucosetolerancewithincreasedmuscleglucoseuptakeintransgenicmiceoverexpressingrxrginskeletalmuscle
AT yasukomanabe increasedsystemicglucosetolerancewithincreasedmuscleglucoseuptakeintransgenicmiceoverexpressingrxrginskeletalmuscle
AT nobuharufujii increasedsystemicglucosetolerancewithincreasedmuscleglucoseuptakeintransgenicmiceoverexpressingrxrginskeletalmuscle
AT takakotakaiigarashi increasedsystemicglucosetolerancewithincreasedmuscleglucoseuptakeintransgenicmiceoverexpressingrxrginskeletalmuscle
AT mikitadaishi increasedsystemicglucosetolerancewithincreasedmuscleglucoseuptakeintransgenicmiceoverexpressingrxrginskeletalmuscle
AT junichirooka increasedsystemicglucosetolerancewithincreasedmuscleglucoseuptakeintransgenicmiceoverexpressingrxrginskeletalmuscle
AT hiroyukiaburatani increasedsystemicglucosetolerancewithincreasedmuscleglucoseuptakeintransgenicmiceoverexpressingrxrginskeletalmuscle
AT tetsuyayamada increasedsystemicglucosetolerancewithincreasedmuscleglucoseuptakeintransgenicmiceoverexpressingrxrginskeletalmuscle
AT hidekikatagiri increasedsystemicglucosetolerancewithincreasedmuscleglucoseuptakeintransgenicmiceoverexpressingrxrginskeletalmuscle
AT saorikakehi increasedsystemicglucosetolerancewithincreasedmuscleglucoseuptakeintransgenicmiceoverexpressingrxrginskeletalmuscle
AT yoshifumitamura increasedsystemicglucosetolerancewithincreasedmuscleglucoseuptakeintransgenicmiceoverexpressingrxrginskeletalmuscle
AT hideokubo increasedsystemicglucosetolerancewithincreasedmuscleglucoseuptakeintransgenicmiceoverexpressingrxrginskeletalmuscle
AT kenichinishida increasedsystemicglucosetolerancewithincreasedmuscleglucoseuptakeintransgenicmiceoverexpressingrxrginskeletalmuscle
AT shinjimiura increasedsystemicglucosetolerancewithincreasedmuscleglucoseuptakeintransgenicmiceoverexpressingrxrginskeletalmuscle
AT osamuezaki increasedsystemicglucosetolerancewithincreasedmuscleglucoseuptakeintransgenicmiceoverexpressingrxrginskeletalmuscle
AT yoshihiroogawa increasedsystemicglucosetolerancewithincreasedmuscleglucoseuptakeintransgenicmiceoverexpressingrxrginskeletalmuscle
_version_ 1718424266985177088