The Stimulus-Secretion Coupling of Glucose-Induced Insulin Release. Cationic and Secretory Effects of Menadione in the Endocrine Pancreas

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Abstract
1 Menadione (2‐methyl‐1,4‐naphoquinone) inhibits isulin release evoked in the rate endocrine pancreas by glucose or glyceraldehyde, but fails to affect the secretroy response to Ca2+, Ba2+, theophylline or gliclzide. The inhibitory effect of menadione upon glucose‐induced insulin relase is a dose‐related, rapid and reversible phenomenon, menadione and glucose acting apparently as competitive antagonists. Menadione affects both the early and talte phase of the secretory resopnse to glucose mesnadione also antagonizes in a dose‐related fashion the ability of glucose to reduce 86Rb efflux, to provoke 86Rb accumulation, to ecause biphasic cahnges in 45Ca efflux and to stimulate 45Ca net uptake in pancreatic islets. 2 It is concluded that menadione imapairs the insulinotopic action of glucose and other rutrients by impeding the remodelling of cationic fluxes normally provoked by these secretagogues in islet cells. Menadione, However, does not affect the capacity of divalent cations to activate the effector system which controls the release of secretory grnules. Meanadione may therefore represent a valuable tool to elucidate the mechanism by which glucose normally modifies the movement of cations in the pancreatic B‐cell.