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Abstract: Glucose-stimulated proinsulin biosynthesis is regulated mainly at the translational level. This study aims at investigating the possible role of the B-cell K+ content in such a process. In order to increase the islet cells K+ content, rat pancreatic islets exposed to a low D-glucose concentration (e.g., 2.5 mM) were incubated in the presence of 30 or 60 mM K+, as distinct from a control extracellular K+ concentration of 5 mM. Under these conditions, the K+ content of the islets, as judged from the net uptake of 86Rb+ over 60 min incubation, was increased to a level comparable to that otherwise found in the presence of 16.7 mM D-glucose. In the presence of 2.5–4.0 mM D-glucose, the rise in K+ concentration from 5 to 30 and 60 mM caused a progressive increase in the incorporation of l-[4-3H]phenylalanine into both all islet peptides and (pro)insulin. A preferential stimulation of proinsulin biosynthesis was only observed in islets incubated at 60 mM K+ in the presence of 4.0 mM D-glucose. In relative terms, the K+-induced increase in biosynthetic variables was less pronounced, however, than that otherwise evoked by a rise in D-glucose concentration from 2.5 to 4.0 mM to 5.6 or 16.7 mM. These findings may suggest that the effect of D-glucose to increase the K+ content of islet cells represents one modality for coupling a rise in D-glucose concentration to stimulation of proinsulin biosynthesis.