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- Title
Glucose- and hormone-induced cAMP oscillations in α- and β-cells within intact pancreatic islets.
- Authors
Tian G; Sandler S; Gylfe E; Tengholm A; Tian, Geng; Sandler, Stellan; Gylfe, Erik; Tengholm, Anders
- Abstract
<bold>Objective: </bold>cAMP is a critical messenger for insulin and glucagon secretion from pancreatic β- and α-cells, respectively. Dispersed β-cells show cAMP oscillations, but the signaling kinetics in cells within intact islets of Langerhans is unknown.<bold>Research Design and Methods: </bold>The subplasma-membrane cAMP concentration ([cAMP](pm)) was recorded in α- and β-cells in the mantle of intact mouse pancreatic islets using total internal reflection microscopy and a fluorescent translocation biosensor. Cell identification was based on the opposite effects of adrenaline on cAMP in α- and β-cells.<bold>Results: </bold>In islets exposed to 3 mmol/L glucose, [cAMP](pm) was low and stable. Glucagon and glucagon-like peptide-1(7-36)-amide (GLP-1) induced dose-dependent elevation of [cAMP](pm), often with oscillations synchronized among β-cells. Whereas glucagon also induced [cAMP](pm) oscillations in most α-cells, <20% of the α-cells responded to GLP-1. Elevation of the glucose concentration to 11-30 mmol/L in the absence of hormones induced slow [cAMP](pm) oscillations in both α- and β-cells. These cAMP oscillations were coordinated with those of the cytoplasmic Ca(2+) concentration ([Ca(2+)](i)) in the β-cells but not caused by the changes in [Ca(2+)](i). The transmembrane adenylyl cyclase (AC) inhibitor 2'5'-dideoxyadenosine suppressed the glucose- and hormone-induced [cAMP](pm) elevations, whereas the preferential inhibitors of soluble AC, KH7, and 1,3,5(10)-estratrien-2,3,17-β-triol perturbed cell metabolism and lacked effect, respectively.<bold>Conclusions: </bold>Oscillatory [cAMP](pm) signaling in secretagogue-stimulated β-cells is maintained within intact islets and depends on transmembrane AC activity. The discovery of glucose- and glucagon-induced [cAMP](pm) oscillations in α-cells indicates the involvement of cAMP in the regulation of pulsatile glucagon secretion.
- Publication
Diabetes, 2011, Vol 60, Issue 5, p1535
- ISSN
0012-1797
- Publication type
journal article
- DOI
10.2337/db10-1087