| First Author | Brown ME | Year | 2025 |
| Journal | Nat Commun | Volume | 16 |
| Issue | 1 | Pages | 5758 |
| PubMed ID | 40593675 | Mgi Jnum | J:370197 |
| Mgi Id | MGI:8218682 | Doi | 10.1038/s41467-025-60831-0 |
| Citation | Brown ME, et al. (2025) Pancreatic islet beta-cell subtypes are derived from biochemically-distinct and nutritionally-regulated islet progenitors. Nat Commun 16(1):5758 |
| abstractText | Endocrine islet beta cells comprise heterogenous subtypes with different gene expression and function levels. Here we study when/how this heterogeneity is induced and how long each subtype maintains its characteristic properties. We show that islet progenitors with distinct gene expression and DNA methylation patterns produce beta-cell subtypes of different secretory function, proliferation rate, and viability in male and female mice. These subtypes have differential gene expression that regulates insulin vesicle production or stimulation-secretion coupling and differential DNA methylation in the putative enhancers of these genes. Maternal obesity, a major diabetes risk factor, reduces the proportion of the beta-cell subtype with higher levels of glucose responsiveness. The gene signature that defines mouse beta-cell subtypes can reliably divide human cells into two sub-populations, with the one having higher predicted glucose responsiveness reduced in diabetic donors. These results suggest that beta-cell subtypes can be derived from islet progenitor subsets modulated by maternal nutrition. |
