The effect of various inhibitors on insulin release from pieces of rabbit pancreas incubated in vitro was studied. Insulin release was stimulated by glucose (3mg./ml.), leucine (5mm), tolbutamide (200μg./ml.), ouabain (10μm), a raised extracellular K+ concentration (60mm) and substitution of the Ca2+ content of the incubation medium by Ba2+ (2·5mm). (a) Mannoheptulose (6mg./ml.) inhibited glucose-stimulated insulin release only. (b) Anoxia abolished or inhibited insulin release stimulated by glucose, leucine, tolbutamide and K+, but had little or no effect on release stimulated by ouabain or Ba2+. (c) 2,4-Dinitrophenol (0·25mm) abolished or inhibited insulin release stimulated by glucose, ouabain or Ba2+. (d) Diazoxide (250μg./ml.) abolished or inhibited insulin release stimulated by glucose, leucine, tolbutamide, ouabain or Ba2+ (0·25 or 1mm). Diazoxide had no effect on insulin release stimulated by Ba2+ (2·5mm) and potentiated release stimulated by K+. (e) Adrenaline (1μm) abolished insulin release stimulated by glucose, leucine, tolbutamide, ouabain or Ba2+. K+-stimulated release was inhibited by adrenaline. (f) Tetrodotoxin (1μm) had no effect on insulin release stimulated by glucose, leucine, tolbutamide, ouabain, K+ or Ba2+. (g) Nupercaine (1mm) abolished insulin release stimulated by glucose or Ba2+.

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