Preproglucagon gene expression in pancreas and intestine diversifies at the level of post-translational processing.

TLDR

Glucagon is a 29‑amino‑acid pancreatic hormone, while the intestinal peptide glicentin is a 69‑amino‑acid form that contains the glucagon sequence flanked by extensions; both arise from a preproglucagon precursor that encodes glucagon and two related peptides separated by an intervening peptide, with each peptide encoded in distinct exons. The study aims to determine whether pancreatic and intestinal glucagon forms arise through alternative RNA and/or protein processing. The authors employed antisera against synthetic glucagon‑like peptides and exon‑specific complementary oligonucleotides to analyze proteins and mRNAs in pancreatic and intestinal extracts. Preproglucagon mRNAs are identical, yet distinct, highly specific peptides are released in pancreas and intestine, with immunocytochemistry revealing colocalization of glucagon and the two glucagon‑like peptides in the same cells, indicating that diversification occurs at the level of cell‑specific post‑translational processing.

Abstract

Glucagon is a pancreatic hormone of 29 amino acids that regulates carbohydrate metabolism and glicentin is an intestinal peptide of 69 amino acids that contains the sequence of glucagon flanked by peptide extensions at the amino and carboxy termini. The glucagon gene encodes a precursor containing glucagon and two additional, structurally related, glucagon-like peptides separated by an intervening peptide. These peptides are encoded in separate exons. To determine whether the pancreatic and intestinal forms of glucagon arise by alternative RNA and/or protein processing, we used antisera to synthetic glucagon-like peptides and exon-specific, complementary oligonucleotides for analyses of proteins and mRNAs in pancreatic and intestinal extracts. Preproglucagon mRNAs are identical, but different and highly specific peptides are liberated in the two tissues. Immunocytochemistry shows colocalization of glucagon and the two glucagon-like peptides in identical cells. We conclude that diversification of preproglucagon gene expression occurs at the level of cell-specific post-translational processing.