C. Saillan-barreau et al., Evidence for a functional role of the cholecystokinin-B/gastrin receptor in the human fetal and adult pancreas, DIABETES, 48(10), 1999, pp. 2015-2021
Gastrin (G) and cholecystokinin (CCK) are gastrointestinal neuropeptides th
at are released into circulation during a meal. G is also transiently expre
ssed during embryogenic and early ontogenic development of the pancreas and
is believed to act on islet-cell. development. Both peptides act on pancre
atic endocrine function; however, the effects are dependent on the species
and on cellular and molecular underlying mechanisms that remain poorly char
acterized. Since CCK-B/G subtype receptor is predominant over the CCK-A sub
type in the human pancreas, me hypothesized that it could be expressed by i
slet cells. Here we present reverse transcription-polymerase chain reaction
and immunohistochemistry data demonstrating that the CCK-B/G receptor is e
xpressed in islet cells and that islet glucagon-producing cells are the maj
or site of CCK-B/G receptor expression in adult and fetal pancreas, Moreove
r, G immunoreactivity was detected in the fetal human pancreas at embryogen
ic week 22, G- and CCK-stimulated glucagon are released from purified human
islets, Concentration of CCK and G eliciting a half-maximal level of gluca
gon secretion were 13 +/- 6 and 8 +/- 5 pmol/l, respectively, Maximal gluca
gon secretion was achieved in the presence of 30 pmol/l peptides and was si
milar to that obtained in the presence of 10 mmol/l L-arginine (1.6 pmol.ml
(-1).90 min(-1)). The nonpeptide antagonist of the CCK-B/G receptor, RPR-10
1048, fully inhibited CCK- and G-stimulated glucagon secretion at 100 nmol/
l concentration. These data are consistent with the view that the CCK-B/G r
eceptor is involved in glucose homeostasis in adult humans and mediates the
autocrine effects of G on islet differentiation and growth in the fetal pa
ncreas.