Proglucagon processing in a rat islet cell line resembles phenotype of intestine rather than pancreas.
Proglucagon, synthesized in the pancreatic islets and the intestinal L-cells, contains in its precursor structure glucagon, glicentin, and two glucagon-like peptides (GLP-I and GLP-II) separated by an intervening peptide (IP-II). We have cloned a stable rat islet cell line expressing the glucagon gene at high levels, thereby allowing us to study the posttranslational processing of proglucagon in this cell line. In contrast to the processing of proglucagon in the pancreas, in which glucagon is liberated, in the cell line we found the intestinal pattern of peptides consisting of glicentin, at least two forms of GLP-I [GLP-I-(1-37) and GLP-I-(7-37)], GLP-II, IP-II, and an amidated form of IP-II. No individually processed glucagon peptide was detected. GLP-I-(1-37), GLP-I-(7-37), GLP-II, IP-II, and IP-II amide coeluted with their respective synthetic peptide standards on gel filtration and ion exchange chromatography. The existence of a single glucagon gene in the rat genome and indistinguishable glucagon mRNAs in pancreas and intestine indicates that the neoplastic transformation that occurred in these islet cells is associated with a phenotypic switch in the differential posttranslational processing of proglucagon to a pattern that mimics that found in the intestinal cells. These observations further support the hypothesis of a common progenitor for the intestinal (L) and islet (A) cells.
D000818:Animals; D002460:Cell Line; D002851:Chromatography, High Pressure Liquid; D005786:Gene Expression Regulation; D005934:Glucagon / Q000235:genetics / Q000378:metabolism*; D004763:Glucagon-Like Peptides; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000166:cytology; D007515:Islets of Langerhans / Q000166:cytology / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism; D052336:Proglucagon; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D051381:Rats
D010455:Peptides; D011498:Protein Precursors; D052336:Proglucagon; D004763:Glucagon-Like Peptides; C015236:glucagon-like-immunoreactivity; D005934:Glucagon