Glucagon- and PP-related peptides of intestinal L cells and pancreatic/gastric A or PP cells. Possible interrelationships of peptides and cells during evolution, fetal development and tumor growth

The immunohistochemical detection of six distinct sequences of proglucagon and its derivatives (GRPP, glicentin, glucagon-37, glucagon-29, GLP₁, GLP₂ and MPGF) in both intestinal L cells and pancreatic or gastric A cells of some mammals (dog, man, guinea pig) confirms that the two cell types produce the same proglucagon molecule, although the final step of its post-translational processing differs in the two cells. Immunohistochemical and ultrastructural patterns of glucagon glicentin cells in the pancreas of lower vertebrates and early human fetuses, as well as tumor cell studies, suggest an evolution of gastropancreatic A cells from L cells. On the contrary, the PP-related peptide PYY of intestinal L cells, and PP with its C-terminal icosapeptide extension of pancreatic PP cells, likely originate from different prohormones. Although intermediate patterns of peptide expression can be observed, including some F-type PP cells of the dog pancreas (uncinate process) and pyloric mucosa showing PYY immunoreactivity or rare PYY and/or HPP immunoreactive cells of the human rectum lacking glicentin reactivity, no obvious relationship can be established between L cells and pancreatic (F-type) PP cells. However, some evolutionary, embryogenetic and oncogenetic link may exist between L cells and human D₁-type PP cells, a minor population of PP cells scattered in the pancreatic tissue of dorsal pouch origin and a major fraction of tumor PP cells.