| First Author | Katsumoto K | Year | 2022 |
| Journal | Nat Commun | Volume | 13 |
| Issue | 1 | Pages | 6255 |
| PubMed ID | 36271049 | Mgi Jnum | J:330537 |
| Mgi Id | MGI:7379637 | Doi | 10.1038/s41467-022-33841-5 |
| Citation | Katsumoto K, et al. (2022) Wnt4 is heterogeneously activated in maturing beta-cells to control calcium signaling, metabolism and function. Nat Commun 13(1):6255 |
| abstractText | Diabetes is a multifactorial disorder characterized by loss or dysfunction of pancreatic beta-cells. beta-cells are heterogeneous, exhibiting different glucose sensing, insulin secretion and gene expression. They communicate with other endocrine cell types via paracrine signals and between beta-cells via gap junctions. Here, we identify the importance of signaling between beta-cells via the extracellular signal WNT4. We show heterogeneity in Wnt4 expression, most strikingly in the postnatal maturation period, Wnt4-positive cells, being more mature while Wnt4-negative cells are more proliferative. Knock-out in adult beta-cells shows that WNT4 controls the activation of calcium signaling in response to a glucose challenge, as well as metabolic pathways converging to lower ATP/ADP ratios, thereby reducing insulin secretion. These results reveal that paracrine signaling between beta-cells is important in addition to gap junctions in controling insulin secretion. Together with previous reports of WNT4 up-regulation in obesity our observations suggest an adaptive insulin response coordinating beta-cells. |
