Development and characterization of experimental β-cell senescence models revealing autophagy defects and altered stimulus-secretion coupling - PubMed
12 hours ago
- #diabetes research
- #β-cell senescence
- #autophagy defects
- Development of a doxorubicin (DOX)-induced senescence model using MIN6 mouse insulinoma β-cell line to study β-cell dysfunction in type 2 diabetes.
- Senescence validated by markers like β-galactosidase positivity, p16INK4a/p21/p53 upregulation, and cell cycle arrest.
- Use of mitochondrial reporters and Insulin-Timer construct to visualize organelle aging and assess β-cell functions.
- Senescent β-cells showed accumulation of mitochondria and insulin granules, defective clearance, and altered Ca2+ influx.
- Despite reduced insulin content, secretion normalized to storage was enhanced, indicating remodeled stimulus-secretion coupling.
- The model highlights autophagy defects as drivers of organelle retention and provides insights into senescence-related β-cell dysfunction.
- The study offers a platform to test interventions targeting senescent-cell burden and to dissect mechanisms of β-cell functional remodeling.