The interaction of various inhibitors and stimuli of insulin release studied with rabbit pancreas in vitro

Abstract

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⁺.