title: Reversibility of β-Cell-Specific Transcript Factors Expression by Long-Term Caloric Restriction in db/db Mouse.
abstract: 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.
authors.affiliation: Department of Endocrinology and Metabolism, Shanghai Tenth People's Hospital, Tongji University, 301 Middle Yanchang Road, Shanghai 200072, China.
authors.forename: Chunjun
authors.initials: C
authors.lastname: Sheng
authors.affiliation: Department of Endocrinology and Metabolism, Shanghai Tenth People's Hospital, Tongji University, 301 Middle Yanchang Road, Shanghai 200072, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Li
authors.affiliation: Department of Endocrinology and Metabolism, Shanghai Tenth People's Hospital, Tongji University, 301 Middle Yanchang Road, Shanghai 200072, China.
authors.forename: Ziwei
authors.initials: Z
authors.lastname: Lin
authors.affiliation: Department of Endocrinology and Metabolism, Shanghai Tenth People's Hospital, Tongji University, 301 Middle Yanchang Road, Shanghai 200072, China.
authors.forename: Manna
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Endocrinology and Metabolism, Shanghai Tenth People's Hospital, Tongji University, 301 Middle Yanchang Road, Shanghai 200072, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Yang
authors.affiliation: Department of Endocrinology and Metabolism, Shanghai Tenth People's Hospital, Tongji University, 301 Middle Yanchang Road, Shanghai 200072, China.
authors.forename: Le
authors.initials: L
authors.lastname: Bu
authors.affiliation: Department of Endocrinology and Metabolism, Shanghai Tenth People's Hospital, Tongji University, 301 Middle Yanchang Road, Shanghai 200072, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Sheng
authors.affiliation: Department of Endocrinology and Metabolism, Shanghai Tenth People's Hospital, Tongji University, 301 Middle Yanchang Road, Shanghai 200072, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Endocrinology and Metabolism, Shanghai Tenth People's Hospital, Tongji University, 301 Middle Yanchang Road, Shanghai 200072, China.
authors.forename: Shen
authors.initials: S
authors.lastname: Qu
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D031204:Caloric Restriction; D054337:Cell Dedifferentiation; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D004195:Disease Models, Animal; D051273:Glucose Transporter Type 2 / Q000235:genetics / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000378:metabolism* / Q000473:pathology; D051473:Maf Transcription Factors, Large / Q000235:genetics / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control*; D010641:Phenotype; D015398:Signal Transduction; D013997:Time Factors; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D051273:Glucose Transporter Type 2; D018398:Homeodomain Proteins; D051473:Maf Transcription Factors, Large; C485160:Mafa protein, mouse; C491328:Nkx6-1 protein, mouse; C495682:Slc2a2 protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors; C084010:pancreatic and duodenal homeobox 1 protein