Skip to Content
Merck
  • Wnt4 is heterogeneously activated in maturing β-cells to control calcium signaling, metabolism and function.

Wnt4 is heterogeneously activated in maturing β-cells to control calcium signaling, metabolism and function.

Nature communications (2022-10-22)
Keiichi Katsumoto, Siham Yennek, Chunguang Chen, Luis Fernando Delgadillo Silva, Sofia Traikov, Dror Sever, Ajuna Azad, Jingdong Shan, Seppo Vainio, Nikolay Ninov, Stephan Speier, Anne Grapin-Botton
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Monoclonal Anti-Glucagon antibody produced in mouse, clone K79bB10, ascites fluid
Sigma-Aldrich
Collagenase from Clostridium histolyticum, Type V, ≥1 FALGPA units/mg solid, >125 CDU/mg solid
Sigma-Aldrich
Anti-Active-β-Catenin (Anti-ABC) Antibody, clone 8E7, clone 8E7, Upstate®, from mouse
Sigma-Aldrich
4-Hydroxytamoxifen, ≥70% Z isomer (remainder primarily E-isomer)