SREBP1c-PAX4 Axis Mediates Pancreatic ß-Cell Compensatory Responses Upon Metabolic Stress.
Diabetes
; 68(1): 81-94, 2019 01.
Article
in En
| MEDLINE
| ID: mdl-30352876
ABSTRACT
SREBP1c is a key transcription factor for de novo lipogenesis. Although SREBP1c is expressed in pancreatic islets, its physiological roles in pancreatic ß-cells are largely unknown. In this study, we demonstrate that SREBP1c regulates ß-cell compensation under metabolic stress. SREBP1c expression level was augmented in pancreatic islets from obese and diabetic animals. In pancreatic ß-cells, SREBP1c activation promoted the expression of cell cycle genes and stimulated ß-cell proliferation through its novel target gene, PAX4 Compared with SREBP1c+/+ mice, SREBP1c-/- mice showed glucose intolerance with low insulin levels. Moreover, ß-cells from SREBP1c-/- mice exhibited reduced capacity to proliferate and secrete insulin. Conversely, transplantation of SREBP1c-overexpressing islets restored insulin levels and relieved hyperglycemia in streptozotocin-induced diabetic animals. Collectively, these data suggest that pancreatic SREBP1c is a key player in mediating ß-cell compensatory responses in obesity.
Full text:
1
Database:
MEDLINE
Main subject:
Homeodomain Proteins
/
Insulin-Secreting Cells
/
Sterol Regulatory Element Binding Protein 1
/
Paired Box Transcription Factors
Limits:
Animals
Language:
En
Journal:
Diabetes
Year:
2019
Type:
Article
Affiliation country:
South Korea