PROGLUCAGON PROCESSING IN ISLET AND INTESTINAL-CELL LINES

To investigate the factors involved in the post-translational processi ng of proglucagon, we have examined the proglucagon-derived peptides ( PGDPs) expressed in normal mouse pancreas and intestine, as well as in both islet (InR1-G9, RIN 1056A) and intestinal (STC-1) cell lines. N- terminal proglucagon processing was similar to that of normal mouse pa ncreas in InR1-G9 cells, but differed in RIN 1056A and STC-1 cells, wh ich contained significant amounts of glucagon as well as the intestina l PGDPs, glicentin and oxyntomodulin. The C-terminal end of proglucago n was processed to small amounts of glucagon-like peptide-1 in InR1-G9 and RIN 1056A cells, as in normal pancreas, while processing was more extensive in both STC-1 cells and normal intestine. Northern blot ana lysis of mRNA transcripts for the prohormone convertases, PC1 and PC2, in the 3 cell lines demonstrated correlations between PC2 and the pre sence of glucagon, as well as between PC1 and production of the intest inal PGDPs. These findings provide support for the suggestion that PC1 and PC2 play roles in the tissue-specific post-translational processi ng of proglucagon.