Submembrane ATP and Ca2+kinetics in α-cells: unexpected signaling for glucagon secretion

• DOI: 10.1096/fj.14-265918
• Publication Date: 2015-04-25T03:41:18Z
• Authors: Jia Li; Qian Yu; Parvin Ahooghalan...; Fiona M. Gribble; Frank Reimann; Anders Tengholm; Erik Gylfe
• Keywords: Pancreatic Islets

Cytoplasmic ATP and Ca(2+) are implicated in current models of glucose's control glucagon insulin secretion from pancreatic α- β-cells, respectively, but little is known about its relation to α-cells. We therefore expressed the fluorescent biosensor Perceval mouse islets loaded them with a indicator. With total internal reflection fluorescence microscopy, we recorded subplasma membrane concentrations ([Ca(2+)]pm; [ATP]pm) superficial β-cells intact related signaling by immunoassay. Consistent ATP's controlling during hypo- hyperglycemia, dose-response relationship for glucose-induced [ATP]pm generation was left shifted α-cells compared β-cells. Both cell types showed [Ca(2+)]pm oscillations opposite phase, probably reflecting energy-consuming transport. Although pulsatile release synchronized same phase between This paradox can be explained overriding stimulation paracrine inhibition, because somatostatin receptor blockade potently stimulated effect on Ca(2+). The data indicate that an α-cell-intrinsic mechanism controls hypoglycemia factors shape hyperglycemia.