Membrane potential-independent effect of Diazoxide on insulin secretion

Background and aims: Glucose-induced insulin secretion is mediated by a bifurcating pathway generating “triggering” and “amplifying” signals. The standard protocol to demonstrate the amplifying effect of glucose (and other nutrient secretagogues) is to depolarize the beta cells by raising the external K+ concentration while the KATP channels are clamped open by Diazoxide to ensure the generation of the Nernst equilibrium. Any further increase in secretion which is caused by the addition of glucose is then believed to be mediated by the still incompletely understood amplifying pathway. Diazoxide, however, has bee…