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- Title
Submembrane ATP and Ca<sup>2+</sup> kinetics in α-cells: unexpected signaling for glucagon secretion.
- Authors
Jia Li; Qian Yu; Ahooghalandari, Parvin; Gribble, Fiona M.; Reimann, Frank; Tengholm, Anders; Gylfe, Erik
- Abstract
Cytoplasmic ATP and Ca2+ are implicated in current models of glucose's control of glucagon and insulin secretion from pancreatic α- and β-cells, respectively, but little is known about ATP and its relation to Ca + in α-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 α- and β-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 glucose-induced [ATP]pm generation was left shifted in α-cells compared to β-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 α- and β-cells. This paradox can be explained by the overriding of Ca2+ stimulation by paracrine inhibition, because somato-statin receptor blockade potently stimulated glucagon release with little effect on Ca2+. The data indicate that an α-cell-intrinsic mechanism controls glucagon in hypoglycemia and that paracrine factors shape pulsatile secretion in hyperglycemia.
- Subjects
GLUCAGON; ADENOSINE triphosphate; PANCREATIC beta cells; BLOOD sugar; IMMUNOASSAY
- Publication
FASEB Journal, 2015, Vol 29, Issue 8, p3379
- ISSN
0892-6638
- Publication type
Article
- DOI
10.1096/fj.14-265918