| First Author | Nasteska D | Year | 2021 |
| Journal | Nat Commun | Volume | 12 |
| Issue | 1 | Pages | 674 |
| PubMed ID | 33514698 | Mgi Jnum | J:301574 |
| Mgi Id | MGI:6504836 | Doi | 10.1038/s41467-020-20632-z |
| Citation | Nasteska D, et al. (2021) PDX1(LOW) MAFA(LOW) beta-cells contribute to islet function and insulin release. Nat Commun 12(1):674 |
| abstractText | Transcriptionally mature and immature beta-cells co-exist within the adult islet. How such diversity contributes to insulin release remains poorly understood. Here we show that subtle differences in beta-cell maturity, defined using PDX1 and MAFA expression, contribute to islet operation. Functional mapping of rodent and human islets containing proportionally more PDX1(HIGH) and MAFA(HIGH) beta-cells reveals defects in metabolism, ionic fluxes and insulin secretion. At the transcriptomic level, the presence of increased numbers of PDX1(HIGH) and MAFA(HIGH) beta-cells leads to dysregulation of gene pathways involved in metabolic processes. Using a chemogenetic disruption strategy, differences in PDX1 and MAFA expression are shown to depend on islet Ca(2+) signaling patterns. During metabolic stress, islet function can be restored by redressing the balance between PDX1 and MAFA levels across the beta-cell population. Thus, preserving heterogeneity in PDX1 and MAFA expression, and more widely in beta-cell maturity, might be important for the maintenance of islet function. |
