title: Glucose- and hormone-induced cAMP oscillations in α- and β-cells within intact pancreatic islets.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Medical Cell Biology, Biomedical Centre, Uppsala University, Uppsala, Sweden.
authors: Geng
authors: G
authors: Tian
authors: Stellan
authors: S
authors: Sandler
authors: Erik
authors: E
authors: Gylfe
authors: Anders
authors: A
authors: Tengholm
mesh_terms: D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004837:Epinephrine / Q000494:pharmacology; D005934:Glucagon / Q000494:pharmacology; D052216:Glucagon-Like Peptide 1 / Q000494:pharmacology; D050416:Glucagon-Secreting Cells / Q000187:drug effects* / Q000378:metabolism*; D005947:Glucose / Q000494:pharmacology*; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism*; D007515:Islets of Langerhans / Q000166:cytology* / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D010084:Oxidation-Reduction / Q000187:drug effects; D010091:Oximes / Q000494:pharmacology
chemical_list: D000067956:Adenylyl Cyclase Inhibitors; D004791:Enzyme Inhibitors; D010091:Oximes; C422418:dibenzo-1,4-dioxine-2-acetyloxime; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D005947:Glucose; D002118:Calcium; D004837:Epinephrine