<em>Wnt4</em> is heterogeneously activated in maturing β-cells to control calcium signaling, metabolism and function
Katsumoto, Keiichi; Yennek, Siham; Chen, Chunguang; Silva, Luis Fernando Delgadillo; Traikov, Sofia; Sever, Dror; Azad, Ajuna; Shan, Jingdong; Vainio, Seppo; Ninov, Nikolay; Speier, Stephan; Grapin-Botton, Anne (2022-10-21)
Katsumoto, K., Yennek, S., Chen, C. et al. Wnt4 is heterogeneously activated in maturing β-cells to control calcium signaling, metabolism and function. Nat Commun 13, 6255 (2022). https://doi.org/10.1038/s41467-022-33841-5
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https://urn.fi/URN:NBN:fi-fe2023062257866
Tiivistelmä
Abstract
Diabetes is a multifactorial disorder characterized by loss or dysfunction of pancreatic β-cells. β-cells are heterogeneous, exhibiting different glucose sensing, insulin secretion and gene expression. They communicate with other endocrine cell types via paracrine signals and between β-cells via gap junctions. Here, we identify the importance of signaling between β-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 β-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 β-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 β-cells.
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