Preserving expression of Pdx1 improves β-cell failure in diabetic mice
| Autor: | Hirotaka Watada, Takeshi Miyatsuka, Hideaki Kaneto, Satomi Takebe, Taka-aki Matsuoka, Iichiro Shimomura, Yuichi Yamamoto, Kazuyuki Miyashita, Fumiyo Kubo, Shugo Sasaki, Naoki Shimo |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Genetically modified mouse endocrine system medicine.medical_specialty Maf Transcription Factors Large endocrine system diseases medicine.medical_treatment Cell Biophysics Mice Transgenic digestive system Biochemistry Diabetes Mellitus Experimental 03 medical and health sciences Transactivation 0302 clinical medicine Internal medicine Diabetes mellitus Insulin-Secreting Cells Glucose Intolerance medicine Animals Insulin Molecular Biology Glucose Transporter Type 2 Homeodomain Proteins geography geography.geographical_feature_category biology Cell Biology medicine.disease Islet Protein Transport 030104 developmental biology medicine.anatomical_structure Endocrinology biology.protein Trans-Activators PDX1 GLUT2 030217 neurology & neurosurgery |
| Zdroj: | Biochemical and biophysical research communications. 483(1) |
| ISSN: | 1090-2104 |
| Popis: | 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 Ins2Akita diabetic mice. Whereas Pdx1 mRNA levels were reduced in Ins2Akita mice compared with their non-diabetic littermates, the mRNA levels of Pdx1 were significantly recovered in the islets of βPdx1; Ins2Akita mice. The βPdx1; Ins2Akita mice exhibited significantly improved glucose tolerance, compared with control Ins2Akita littermates, accompanied by increased insulin secretion after glucose loading. Furthermore, histological examination demonstrated that βPdx1; Ins2Akita mice had improved localization of SLC2A2 (GLUT2), and quantitative RT-PCR showed the recovered expression of Mafa and Gck mRNAs in the islets of βPdx1; Ins2Akita mice. These findings suggest that the sustained expression of Pdx1 improves β-cell failure in Ins2Akita mice, at least partially through the preserving expression of β-cell-specific genes as well as improved localization of GLUT2. |
| Databáze: | OpenAIRE |
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