Expression of the insulin gene is regulated by opioid peptides.

The effects of the opioid peptides Met- and Leu-enkephalin on the expression of the insulin gene in isolated adult rat islets of Langerhans were examined. Isolated rat islets were maintained under various culture conditions for 26 h. The contents of islet preproinsulin mRNA and the amounts of (pro)insulin biosynthesis were assayed. In the presence of 5 mM glucose the preproinsulin mRNA content was increased by 10(-8) M Met-enkephalin to 198% (p less than 0.001) and by Leu-enkephalin to 145% (p less than 0.001) of the control without enkephalins. The preproinsulin mRNA content was raised in the presence of 5 mM glucose by 10(-10) M significant. These results corresponded with an increase in the (pro)insulin biosynthesis under the same conditions. The biosynthesis of (pro)insulin was strongly decreased by actinomycin D at the glucose and enkephalin concentrations tested. The results demonstrated that there is a dose-dependent stimulation of the insulin gene expression by enkephalins and that the increase in (pro)insulin biosynthesis in isolated pancreatic islets by endogenous opioid peptides occurs mainly on the pretranslational level.