Figure 1.

A schematic overview of tissue-specific proglucagon processing in the gut/brain (A) and in the pancreas (B). The proglucagon gene, located on chromosome 2 and comprised of 6 exons, is transcribed to generate proglucagon messenger RNA (mRNA). Proglucagon mRNA is subsequently translated to yield the 158 residue, precursor protein, proglucagon. In enteroendocrine L-cells of the ileum and colon (A) proglucagon is processed by prohormone convertase 1/3 (PC1/3) to generate glicentin, oxyntomodulin, glucagon-like peptides-1 and -2 (GLP-1, GLP-2) and intervening peptide-2 (IP-2). Conversely, in pancreatic alpha-cells (B), post-translational modification by prohormone convertase 2 (PC2) is responsible for the generation of the major proglucagon fragment (MPGF), glucagon, glicentin-related pancreatic polypeptide (GRPP) and intervening peptide-1 (IP-1).