SREBP1c-PAX4 Axis Mediates Pancreatic β-Cell Compensatory Responses Upon Metabolic Stress.
Gung LeeHagoon JangYe Young KimSung Sik ChoeJinuk KongInjae HwangJeu ParkSeung-Soon ImJae Bum KimPublished in: Diabetes (2018)
SREBP1c is a key transcription factor for de novo lipogenesis. Although SREBP1c is expressed in pancreatic islets, its physiological roles in pancreatic β-cells are largely unknown. In this study, we demonstrate that SREBP1c regulates β-cell compensation under metabolic stress. SREBP1c expression level was augmented in pancreatic islets from obese and diabetic animals. In pancreatic β-cells, SREBP1c activation promoted the expression of cell cycle genes and stimulated β-cell proliferation through its novel target gene, PAX4 Compared with SREBP1c+/+ mice, SREBP1c-/- mice showed glucose intolerance with low insulin levels. Moreover, β-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 β-cell compensatory responses in obesity.
Keyphrases
- type diabetes
- cell cycle
- cell proliferation
- high fat diet induced
- transcription factor
- induced apoptosis
- cell therapy
- single cell
- poor prognosis
- metabolic syndrome
- diabetic rats
- weight loss
- genome wide
- adipose tissue
- oxidative stress
- endoplasmic reticulum stress
- physical activity
- endothelial cells
- body mass index
- bone marrow
- binding protein
- deep learning
- electronic health record
- high glucose