Synchronizing Ca2+ and cAMP oscillations in pancreatic β-cells: a role for glucose metabolism and GLP-1 receptors?Focus on “Regulation of cAMP dynamics by Ca2+ and G protein-coupled receptors in the pancreatic β-cell: a computational approach”

THE HORMONAL ACTIVATION of cAMP production in pancreatic β-cells is accompanied by an increase of cytosolic [cAMP] that can be measured in real time through the use of a cAMP sensor (Epac1-camps) that exhibits a decrease of fluorescence resonance energy transfer (FRET) when it binds to cAMP (9,15,18).When this cAMP sensor is paired with the fluorescent Ca 2+ indicator fura-2, it is possible to perform simultaneous measurements of cytosolic [cAMP] and [Ca 2+ ] in single living β-cells (9).Studies performed in this manner have revealed oscillations in the levels of both second messengers, a phenomenon that can be imaged to evaluate the spatial distribution and temporal dynamics of cAMP and Ca 2+ (15).Fridlyand et al. ( 6) now report a new mathematical model that seeks to explain how oscillations of cAMP and Ca 2+ are generated.A primary focus of the model is glucagon-like peptide-1 (GLP-1), a blood glucose-lowering hormone that stimulates β-cell cAMP production and that also potentiates glucose-stimulated insulin secretion (4,7,(12)(13)(14).An additional focus of the model concerns D-glucose, a metabolizable sugar that increases the cytosolic [Ca 2+ ] of β-cells and that is generally considered to be the primary physiological stimulus regulating β-cell insulin secretion (11).The computational approach devised by Fridlyand et al. is of interest because it may help resolve a long-standing debate within the field of endocrinology: specifically, how do GLP-1 and glucose metabolism interact to stimulate insulin secretion from β-cells?