Glucagon-like peptide 1 and peptide YY are in separate storage organelles in enteroendocrine cells

A sub-group of enteroendocrine cells (L cells) release
gastrointestinal hormones, GLP-1 and PYY, which have
different but overlapping physiological effects, in response to
intraluminal nutrients. Whilst their release profiles are not
identical, how the plasma levels of these two hormones are
differentially regulated is not well understood. We investigate
the possibility that GLP-1 and PYY are in separate storage
vesicles. In this study, the subcellular location of GLP-1 and
PYY storage organelles is investigated using double-labelling
immunohistochemistry, super resolution microscopy and
high-resolution confocal microscopy. In all species tested,
human, pig, rat and mouse, most cytoplasmic stores that
exhibited GLP-1 or PYY immunofluorescence were distinct
from each other. The volume occupancy, determined by 3D
analysis, overlapped by only about 10∼20 %. At the lower
resolution achieved by conventional confocal microscopy,
there was also evidence of GLP-1 and PYY being in separate
storage compartments but, in subcellular regions where there
were many storage vesicles, separate storage could not be
resolved. The results indicate that different storage vesicles
in L cells contain predominantly GLP-1 or predominantly
PYY. Whether GLP-1 and PYY storage vesicles are selectively mobilised and their products are selectively released
needs to be determined.