Pancreatic islets contain alpha-, beta-, gamma- and delta-cells as sensors and actuators regulating glucose homeostasis. Despite the known importance of alpha-cells, they are seemingly required for glucose tolerance only under metabolic stress. In an inducible model of alpha-cell ablation in mice (GluDTR), glucose tolerance was considerably decreased by physiological addition of amino-acids mimicking meals. Analysis of islet beta-cell secretion and electrical activities using microelectrode arrays (MEA) detected only minor differences in GluDTR mice for glucose but revealed a major reduction upon addition of amino acids. Analysis of functional islet beta-cell networks by high density MEA revealed leading 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, alpha-cells are required for nutrient homeostasis by regulating the dynamics of beta-cell networks.
Lallouet et al. (Wed,) studied this question.