Thiopentone-induced insulin secretion via activation of IP3-sensitive calcium stores in rat pancreatic beta cells

【摘要】：正Although glucose-elicited insulin secretion depends on Ca~(2+) entry through voltage-gated Ca~(2+) channels in the cell membrane of pancreatic beta cells,there are also ample evidence for an important role of intracellular Ca~(2+) stores,particularly in relation to biochemical stimulus.We report here that thiopentone stimulates insulin secretion from cultured primary rat pancreatic beta cells,and the mechanisms were investigated by measurements of whole-cell K~+ and Ca~(2+) currents,membrane potential,the cytoplasmic Ca~(2+) concentration([Ca~(2+)];) and membrane capacitance. Thiopentone(300μmol/L) reduces both whole-cell K~+ currents and Ca~(2+) currents to 60%,while it only depolarizes beta cell membrane potential in 20%pancreatic beta cells.In the meantime,the anesthetic evokes[Ca~(2+)]_i increase in beta cells in the presence or absence of extracellular calcium.These data indicate that thiopentone-induced insulin release occurs by mechanisms that are independent of Ca~(2+) entry across the cell membrane.The thiopentone-induced [Ca~(2+)]_i rise in cultured rat beta cells is sensitive to heparin(0.1 mg/mL),a drug that inhibits the binding of IP3 and IP3 receptor;thapsigargin(1μmol/L),a blocker of the endoplasmic reticulum(ER) Ca~(2+) pump;and U73122,a PLC inhibitor.We conclude that the[Ca~(2+)];required for thiopentone-induced insulin secretion is released from IP3-sensitive Ca~(2+) store.