Submembrane ATP and Ca2+ kinetics in alpha-cells: unexpected signaling for glucagon secretion
2015 (English)In: The FASEB Journal, ISSN 0892-6638, E-ISSN 1530-6860, Vol. 29, no 8, 3379-3388 p.Article in journal (Refereed) Published
Cytoplasmic ATP and Ca2+ are implicated in current models of glucose's control of glucagon and insulin secretion from pancreatic alpha- and beta-cells, respectively, but little is known about ATP and its relation to Ca2+ in alpha-cells. We therefore expressed the fluorescent ATP biosensor Perceval in mouse pancreatic islets and loaded them with a Ca2+ indicator. With total internal reflection fluorescence microscopy, we recorded subplasma membrane concentrations of Ca2+ and ATP ([Ca2+](pm); [ATP](pm)) in superficial alpha- and beta-cells of intact islets and related signaling to glucagon and insulin secretion by immunoassay. Consistent with ATP's controlling glucagon and insulin secretion during hypo- and hyperglycemia, respectively, the dose-response relationship for glucoseinduced [ATP](pm) generation was left shifted in alpha-cells compared to beta-cells. Both cell types showed [Ca2+](pm) and [ATP](pm) oscillations in opposite phase, probably reflecting energy-consuming Ca2+ transport. Although pulsatile insulin and glucagon release are in opposite phase, [Ca2+](pm) synchronized in the same phase between alpha- and beta-cells. This paradox can be explained by the overriding of Ca2+ stimulation by paracrine inhibition, because somatostatin receptor blockade potently stimulated glucagon release with little effect on Ca2+. The data indicate that an alpha-cell-intrinsic mechanism controls glucagon in hypoglycemia and that paracrine factors shape pulsatile secretion in hyperglycemia.
Place, publisher, year, edition, pages
2015. Vol. 29, no 8, 3379-3388 p.
oscillations, islet of Langerhans, signal transduction, paracrine
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy) Cell and Molecular Biology
IdentifiersURN: urn:nbn:se:uu:diva-261252DOI: 10.1096/fj.14-265918ISI: 000358796900025PubMedID: 25911612OAI: oai:DiVA.org:uu-261252DiVA: diva2:850314
FunderSwedish Diabetes AssociationSwedish Research CouncilNovo Nordisk