title: Islet beta-cell secretion determines glucagon release from neighbouring alpha-cells.
abstract: Homeostasis of blood glucose is maintained by hormone secretion from the pancreatic islets of Langerhans. Glucose stimulates insulin secretion from beta-cells but suppresses the release of glucagon, a hormone that raises blood glucose, from alpha-cells. 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 process. 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 alpha- and beta-cells. We find that pyruvate, a glycolytic intermediate and principal substrate of mitochondria, stimulates glucagon secretion. Our analyses indicate that, although alpha-cells, like beta-cells, possess the inherent capacity to respond to nutrients, secretion from alpha-cells is normally suppressed by the simultaneous activation of beta-cells. Zinc released from beta-cells may be implicated in this suppression. Our results define the fundamental mechanisms of differential responses to identical stimuli between cells in a microorgan.
authors.affiliation: Division of Clinical Biochemistry, Department of Internal Medicine, University Medical Center, 1211 Geneva 4, Switzerland.
authors.forename: Hisamitsu
authors.initials: H
authors.lastname: Ishihara
authors.forename: Pierre
authors.initials: P
authors.lastname: Maechler
authors.forename: Asllan
authors.initials: A
authors.lastname: Gjinovci
authors.forename: Pedro-Luis
authors.initials: PL
authors.lastname: Herrera
authors.forename: Claes B
authors.initials: CB
authors.lastname: Wollheim
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000502:physiology; D020013:Calcium Signaling / Q000502:physiology; D002450:Cell Communication / Q000502:physiology*; D002478:Cells, Cultured; D005934:Glucagon / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology; D006019:Glycolysis / Q000502:physiology; D006706:Homeostasis / Q000502:physiology; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D019289:Pyruvic Acid / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000502:physiology; D015032:Zinc / Q000378:metabolism / Q000494:pharmacology
chemical_list: D001786:Blood Glucose; D007328:Insulin; D019289:Pyruvic Acid; D000255:Adenosine Triphosphate; D005934:Glucagon; D005947:Glucose; D015032:Zinc