title: Preserving expression of Pdx1 improves β-cell failure in diabetic mice.
abstract: Pdx1, a β-cell-specific transcription factor, has been shown to play a crucial role in maintaining β-cell function through transactivation of β-cell-related genes. In addition, it has been reported that the expression levels of Pdx1 are compromised under diabetic conditions in human and rodent models. We therefore aimed to clarify the possible beneficial role of Pdx1 against β-cell failure and generated the transgenic mouse that expressed Pdx1 conditionally and specifically in β cells (βPdx1) and crossed these mice with Ins2Akitadiabetic mice. Whereas Pdx1 mRNA levels were reduced in Ins2Akitamice compared with their non-diabetic littermates, the mRNA levels of Pdx1 were significantly recovered in the islets of βPdx1; Ins2Akitamice. The βPdx1; Ins2Akitamice exhibited significantly improved glucose tolerance, compared with control Ins2Akitalittermates, accompanied by increased insulin secretion after glucose loading. Furthermore, histological examination demonstrated that βPdx1; Ins2Akitamice had improved localization of SLC2A2 (GLUT2), and quantitative RT-PCR showed the recovered expression of Mafa and Gck mRNAs in the islets of βPdx1; Ins2Akitamice. These findings suggest that the sustained expression of Pdx1 improves β-cell failure in Ins2Akitamice, at least partially through the preserving expression of β-cell-specific genes as well as improved localization of GLUT2.
authors.affiliation: Department of Metabolic Medicine, Osaka University, Graduate School of Medicine, Osaka, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Yamamoto
authors.affiliation: Department of Metabolic Medicine, Osaka University, Graduate School of Medicine, Osaka, Japan; Department of Metabolism and Endocrinology, Juntendo University, Graduate School of Medicine, Tokyo, Japan. Electronic address: miyatsuka-takeshi@umin.net.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Miyatsuka
authors.affiliation: Department of Metabolic Medicine, Osaka University, Graduate School of Medicine, Osaka, Japan.
authors.forename: Shugo
authors.initials: S
authors.lastname: Sasaki
authors.affiliation: Department of Metabolic Medicine, Osaka University, Graduate School of Medicine, Osaka, Japan.
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Miyashita
authors.affiliation: Department of Metabolic Medicine, Osaka University, Graduate School of Medicine, Osaka, Japan.
authors.forename: Fumiyo
authors.initials: F
authors.lastname: Kubo
authors.affiliation: Department of Metabolic Medicine, Osaka University, Graduate School of Medicine, Osaka, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Shimo
authors.affiliation: Department of Metabolic Medicine, Osaka University, Graduate School of Medicine, Osaka, Japan.
authors.forename: Satomi
authors.initials: S
authors.lastname: Takebe
authors.affiliation: Department of Metabolism and Endocrinology, Juntendo University, Graduate School of Medicine, Tokyo, Japan.
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Watada
authors.affiliation: Department of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, Okayama, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Kaneto
authors.affiliation: Department of Metabolic Medicine, Osaka University, Graduate School of Medicine, Osaka, Japan.
authors.forename: Taka-Aki
authors.initials: TA
authors.lastname: Matsuoka
authors.affiliation: Department of Metabolic Medicine, Osaka University, Graduate School of Medicine, Osaka, Japan.
authors.forename: Iichiro
authors.initials: I
authors.lastname: Shimomura
mesh_terms: D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000235:genetics / Q000473:pathology*; D018149:Glucose Intolerance / Q000235:genetics; D051273:Glucose Transporter Type 2 / Q000235:genetics / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D007328:Insulin / Q000235:genetics; D050417:Insulin-Secreting Cells / Q000378:metabolism / Q000473:pathology*; D051473:Maf Transcription Factors, Large / Q000235:genetics / Q000378:metabolism; D008822:Mice, Transgenic; D021381:Protein Transport; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*
chemical_list: D051273:Glucose Transporter Type 2; D018398:Homeodomain Proteins; C561967:Ins2 protein, mouse; D007328:Insulin; D051473:Maf Transcription Factors, Large; C485160:Mafa protein, mouse; C495682:Slc2a2 protein, mouse; D015534:Trans-Activators; C084010:pancreatic and duodenal homeobox 1 protein
keywords: Diabetes; GLUT2; Ins2(Akita) mouse; Pdx1