Distinct intracellular Ca2+ response to extracellular adenosine triphosphate in pancreatic beta-cells in rats and mice.

Extracellular adenosine triphosphate (ATP) has distinct effects on insulin secretion from pancreatic beta-cells between rats and mice. Using a confocal microscope, we compared changes between rats and mice in cytosolic free calcium concentration ([Ca2+]c) in pancreatic beta-cells stimulated by extracellular ATP. Extracellular ATP (50 microM) induced calcium release from intracellular calcium stores by activating P2Y receptors in both rat and mouse beta-cells. The intracellular calcium release stimulated by extracellular ATP is significantly smaller in amplitude and longer in duration in rat beta-cells than in mouse. In response to extracellular ATP, rat beta-cells activate store-operated calcium entry following intracellular calcium release. This response is lacking in mouse beta-cells. Rat and mouse beta-cells both responded to 9 mM glucose by increasing [Ca2+]c. This increase, however, was pronounced only in the rat beta-cells. In 9 mM glucose, extracellular ATP induced a pronounced calcium release above the increased level of [Ca2+]c in rat beta-cells. In mouse beta-cells, however, extracellular ATP did not exhibit calcium release on top of the increased level of [Ca2+]c in 9 mM glucose. These results demonstrate distinct responses between rat and mouse beta-cells to extracellular ATP under the condition of low and high glucose. Considering that extracellular ATP inhibits insulin secretion from mouse beta-cells but stimulates insulin secretion from rat beta-cells, we suggest that store-operated Ca2+ entry may be related to exocytosis in pancreatic rat beta-cells.