Manganese action on protein synthesis in diabetic rat pancreas: evidence for a possible physiological role.

The actions of manganese on [3H]phenylalanine incorporation into pancreatic acinar protein from streptozotocin-diabetic rats were compared with the actions of several divalent cations, insulin, and pancreatic secretagogues. In the presence of Ca2+, 7 X 10(-4) M manganese greatly enhanced [3H]phenylalanine incorporation. Under similar incubation conditions, magnesium exerted only a slight stimulatory effect on incorporation, whereas cobalt and nickel failed to enhance incorporation. Removal of Ca2+ from incubation medium, or replacement of Ca2+ by either barium or strontium, abolished the stimulatory effect of manganese on incorporation. Lanthanum, at a concentration that inhibits stimulated Ca2+ influx in acini (10(-4) M), also blocked the stimulatory effect of manganese but did not alter the actions of insulin on incorporation. Dibutyryl cyclic GMP, a competitive antagonist of cholecystokinin-octapeptide, and atropine, a competitive antagonist of carbachol, blocked the stimulatory effects of the respective secretagogues on incorporation. Neither antagonist altered the actions of manganese. These findings suggest that in the face of insulin deficiency manganese enhances pancreatic protein synthesis in diabetic rats via a Ca2+-dependent mechanism that is distinct from the actions of other divalent cations, insulin and pancreatic secretagogues.