Nature Cell Biology
- 5, 330 - 335 (2003)
Published online: 17 March 2003; | doi:10.1038/ncb951
Islet  -cell secretion determines glucagon release from neighbouring  -cellsHisamitsu Ishihara1, Pierre Maechler1, Asllan Gjinovci1, Pedro-Luis Herrera2 & Claes B. Wollheim11
Division of Clinical Biochemistry, Department of Internal Medicine, University Medical Center, 1211 Geneva 4, Switzerland
2
Department of Morphology, University Medical Center, 1211 Geneva 4, Switzerland
Correspondence should be addressed to Claes B. Wollheim claes.wollheim@medicine.unige.ch Homeostasis of blood glucose is maintained by hormone secretion from the pancreatic islets of Langerhans. Glucose stimulates insulin secretion from  -cells but suppresses the release of glucagon, a hormone that raises blood glucose, from  -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 - and -cells. We find that pyruvate, a glycolytic intermediate and principal substrate of mitochondria, stimulates glucagon secretion. Our analyses indicate that, although -cells, like -cells, possess the inherent capacity to respond to nutrients, secretion from -cells is normally suppressed by the simultaneous activation of -cells. Zinc released from -cells may be implicated in this suppression. Our results define the fundamental mechanisms of differential responses to identical stimuli between cells in a microorgan.
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