Effect of cations on insulin biosynthesis in mouse pancreatic islets

Rates of incorporation of L-phenyl(2,3-3H)alanine into insulin and total protein in mouse pancreatic islets were measured. Glucose-stimulated total protein synthesis and insulin biosynthesis are depressed when the medium is deprived of Na+, K+ and Mg++ whereas the same processes are totally independent of extracellular Ca++. Excess Ca++ (15 mM) has no effect on insulin biosynthesis but 12 mM Mg++ impairs glucose-stimulated insulin biosynthesis preferentially. 40 mM K+ inhibits glucose-stimulated insulin biosynthesis as well as total protein synthesis. Omission of K+ inhibits glucose-stimulated insulin biosynthesis preferentially. 10(-4) M ouabain inhibits both glucose-stimulated total protein synthesis and insulin biosynthesis. When Ca++ is replaced by 2 mM Ba++ glucose-stimulation of both total protein synthesis and insulin synthesis is abolished. Preferentially inhibited insulin biosynthesis in the presence of very low Na+ (24 mM) is seen not only with glucose but also with leucine, N-acetylglucosamine and mannose as stimulants, suggesting that the sodium-sensitive step is localized distal to the process of glucose recognition by the beta-cell.