Islet β-cell secretion determines glucagon release from neighbouring α-cells

Abstract

Homeostasis of blood glucose is maintained by hormone secretion from the pancreatic islets of Langerhans. Glucose stimulates insulin secretion from β-cells but suppresses the release of glucagon, a hormone that raises blood glucose, from α-cells¹. The mechanism by which nutrients stimulate insulin secretion has been studied extensively: ATP has been identified as the main messenger and the ATP-sensitive potassium channel as an essential transducer in this process². By contrast, much less is known about the mechanisms by which nutrients modulate glucagon secretion. Here we use conventional pancreas perfusion and a transcriptional targeting strategy to analyse cell-type-specific signal transduction and the relationship between islet α- and β-cells. We find that pyruvate, a glycolytic intermediate and principal substrate of mitochondria, stimulates glucagon secretion. Our analyses indicate that, although α-cells, like β-cells, possess the inherent capacity to respond to nutrients, secretion from α-cells is normally suppressed by the simultaneous activation of β-cells. Zinc released from β-cells may be implicated in this suppression. Our results define the fundamental mechanisms of differential responses to identical stimuli between cells in a microorgan.