title: Glucose Evokes Rapid Ca2+ and Cyclic AMP Signals by Activating the Cell-Surface Glucose-Sensing Receptor in Pancreatic β-Cells.
abstract: Glucose is a primary stimulator of insulin secretion in pancreatic β-cells. High concentration of glucose has been thought to exert its action solely through its metabolism. In this regard, we have recently reported that glucose also activates a cell-surface glucose-sensing receptor and facilitates its own metabolism. In the present study, we investigated whether glucose activates the glucose-sensing receptor and elicits receptor-mediated rapid actions. In MIN6 cells and isolated mouse β-cells, glucose induced triphasic changes in cytoplasmic Ca(2+) concentration ([Ca(2+)]c); glucose evoked an immediate elevation of [Ca(2+)]c, which was followed by a decrease in [Ca(2+)]c, and after a certain lag period it induced large oscillatory elevations of [Ca(2+)]c. Initial rapid peak and subsequent reduction of [Ca(2+)]c were independent of glucose metabolism and reproduced by a nonmetabolizable glucose analogue. These signals were also blocked by an inhibitor of T1R3, a subunit of the glucose-sensing receptor, and by deletion of the T1R3 gene. Besides Ca(2+), glucose also induced an immediate and sustained elevation of intracellular cAMP ([cAMP]c). The elevation of [cAMP]c was blocked by transduction of the dominant-negative Gs, and deletion of the T1R3 gene. These results indicate that glucose induces rapid changes in [Ca(2+)]c and [cAMP]c by activating the cell-surface glucose-sensing receptor. Hence, glucose generates rapid intracellular signals by activating the cell-surface receptor.
authors.affiliation: Department of Cell Biology, Institute for Molecular & Cellular Regulation, Gunma University, Maebashi, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Nakagawa
authors.affiliation: Department of Cell Biology, Institute for Molecular & Cellular Regulation, Gunma University, Maebashi, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Nagasawa
authors.affiliation: Department of Cell Biology, Institute for Molecular & Cellular Regulation, Gunma University, Maebashi, Japan.
authors.forename: Johan
authors.initials: J
authors.lastname: Medina
authors.affiliation: Department of Cell Biology, Institute for Molecular & Cellular Regulation, Gunma University, Maebashi, Japan.
authors.forename: Itaru
authors.initials: I
authors.lastname: Kojima
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D051379:Mice; D011956:Receptors, Cell Surface / Q000378:metabolism*
chemical_list: D007328:Insulin; D011956:Receptors, Cell Surface; D000242:Cyclic AMP; D005947:Glucose; D002118:Calcium