Glucose Evokes Rapid Ca2 and Cyclic AMP Signals by Activating the Cell-Surface Glucose-Sensing Receptor in Pancreatic β-CellsReportar como inadecuado




Glucose Evokes Rapid Ca2 and Cyclic AMP Signals by Activating the Cell-Surface Glucose-Sensing Receptor in Pancreatic β-Cells - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

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 Ca2+ concentration Ca2+c; glucose evoked an immediate elevation of Ca2+c, which was followed by a decrease in Ca2+c, and after a certain lag period it induced large oscillatory elevations of Ca2+c. Initial rapid peak and subsequent reduction of Ca2+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 Ca2+, glucose also induced an immediate and sustained elevation of intracellular cAMP cAMPc. The elevation of cAMPc was blocked by transduction of the dominant-negative Gs, and deletion of the T1R3 gene. These results indicate that glucose induces rapid changes in Ca2+c and cAMPc by activating the cell-surface glucose-sensing receptor. Hence, glucose generates rapid intracellular signals by activating the cell-surface receptor.



Autor: Yuko Nakagawa, Masahiro Nagasawa, Johan Medina, Itaru Kojima

Fuente: http://plos.srce.hr/



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