Pancreatic α cells are required for nutrient homeostasis by regulating dynamic β cell networks in islets

Pancreatic islets contain α, β, γ, and δ cells as sensors and actuators regulating glucose homeostasis. Despite the known importance of α cells, they are seemingly required for glucose tolerance only under metabolic stress. In an inducible model of α cell ablation in mice (GluDTR), glucose tolerance was considerably decreased by the addition of amino acids mimicking meals. Analysis of islet β cell secretion and electrical activities using microelectrode arrays (MEAs) detected only minor differences in GluDTR mice for glucose but revealed a major reduction upon addition of amino acids. Analysis of functional islet β cell networks by high-density MEA revealed leader regions in different locations, a high degree of synchrony, and the activation of large cell clusters. The characteristics of leading regions were preserved in GluDTR islets, but synchrony, cluster size, and signal propagation speed were largely reduced. Thus, even without metabolic stress, α cells are required for nutrient homeostasis by regulating the dynamics of β cell networks.