The effect of cations on insulin release was studied in the isolated pancreas of the rat perfused with a synthetic perfusate consisting of albumin and buffer. The omission of calcium and magnesium ion completely inhibited insulin release stimulated by glucose. The ionic requirement was specific for calcium ion since perfusates containing calcium but no magnesium permitted normal insulin release by glucose, whereas perfusates containing magnesium but no calcium did not. The presence of only 0.2 mEq. per liter calcium was adequate to permit much, though not all, of the insulin response after glucose to occur. Potassium ion, when raised from 4 to 8 mEq. per liter, directly stimulated insulin release in the complete absence of glucose.

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