Reversibility of β-Cell-Specific Transcript Factors Expression by Long-Term Caloric Restriction in db/db Mouse

• Published in: Journal of diabetes research 2016-01, Vol.2016 (2016), p.1-11
• Main Authors: Qu, Shen, Li, Hong, Bu, Le, Yang, Peng, Zhang, Manna, Lin, Ziwei, Li, Feng, Sheng, Chun-Jun, Sheng, Hui
• Format: Article
• Language: English
• Subjects: Age; Animals; Antibodies; Biomarkers - blood; Blood Glucose - metabolism; Caloric Restriction; Cell Dedifferentiation; Diabetes; Diabetes Mellitus, Type 2 - genetics; Diabetes Mellitus, Type 2 - metabolism; Diabetes Mellitus, Type 2 - pathology; Diabetes Mellitus, Type 2 - prevention & control; Disease Models, Animal; Experiments; Gene expression; Glucose; Glucose Transporter Type 2 - genetics; Glucose Transporter Type 2 - metabolism; Homeodomain Proteins - genetics; Homeodomain Proteins - metabolism; Insulin; Insulin-Secreting Cells - metabolism; Insulin-Secreting Cells - pathology; Laboratory animals; Maf Transcription Factors, Large - genetics; Maf Transcription Factors, Large - metabolism; Male; Mice, Inbred C57BL; Obesity - genetics; Obesity - metabolism; Obesity - prevention & control; Phenotype; Signal Transduction; Software; Time Factors; Trans-Activators - genetics; Trans-Activators - metabolism; Transcription factors; Transcription Factors - genetics; Transcription Factors - metabolism
• ISSN: 2314-6745; 2314-6753
• DOI: 10.1155/2016/6035046

Type 2 diabetes (T2D) is characterized by β-cell dedifferentiation, but underlying mechanisms remain unclear. The purpose of the current study was to explore the mechanisms of β-cell dedifferentiation with and without long-term control of calorie intake. We used a diabetes mouse model (db/db) to analyze the changes in the expression levels of β-cell-specific transcription factors (TFs) and functional factors with long-term caloric restriction (CR). Our results showed that chronic euglycemia was maintained in the db/db mice with long-term CR intervention, and β-cell dedifferentiation was significantly reduced. The expression of Glut2, Pdx1, and Nkx6.1 was reversed, while MafA expression was significantly increased with long-term CR. GLP-1 pathway was reactivated with long-term CR. Our work showed that the course of β-cell dedifferentiation can intervene by long-term control of calorie intake. Key β-cell-specific TFs and functional factors play important roles in maintaining β-cell differentiation. Targeting these factors could optimize T2D therapies.