R. Guimbaud et al., INTRADUODENAL FREE FATTY-ACIDS RATHER THAN TRIGLYCERIDES ARE RESPONSIBLE FOR THE RELEASE OF CCK IN HUMANS, Pancreas, 14(1), 1997, pp. 76-82
Exocrine pancreas from different species behaves differently in respon
se to the presence of intact or digested nutrients in the duodenum. A
failure of cholecystokinin (CCK) release after a meal has been shown a
mong patients with exocrine pancreatic insufficiency. This abnormality
could be restored by the administration of pancreatic extracts, sugge
sting that digested rather than intact nutrients are responsible for t
he release of CCK and subsequently gallbladder contraction in humans.
The aim of this study was to determine the specific role of different
lipidic stimuli in humans. Seven male patients (mean age, 52 years) wi
th pancreatic insufficiency secondary to chronic pancreatitis were sel
ected. Pancreatic insufficiency was considered severe in five of them
(lipase output, <1.000 IU/min) and moderate in another two (lipase out
put, >1.000 and <2.300 IU/min). Plasma CCK (by bioassay), gallbladder
contraction (by ultrasound), and enzyme output (chymotrypsin) in respo
nse to duodenal administration of either oleic acid as free fatty acid
s or 20% Intralipid as triglycerides were measured in each patient wit
h at least a 48-h interval between each test. In all these patients wi
th pancreatic in insufficiency, duodenal perfusion of foe fatty acids
generated a more pronounced (91 +/- 11 vs. 49 +/- 21 pM) and faster (1
5 vs. 30 min) (p < 0.05) CCK release than triglycerides. Furthermore,
gallbladder contraction was more efficient when free fatty acids inste
ad of triglycerides were administered in the duodenum (86 +/- 5 vs. 69
+/- 4%) at 10 min (p < 0.05) and (73 +/- 8 vs. 51 +/- 5%) at 15 min (
p < 0.03). Among patients with measurable residual pancreatic function
, enzyme outputs were shown to be higher during free fatty acid than t
riglyceride perfusion. In humans, free fatty acids rather than triglyc
erides, when present in the duodenum, stimulate CCK release and gallbl
adder contraction. in patients with moderate pancreatic insufficiency
this phenomenon may increase residual enzymatic secretion. These resul
ts allow us to encourage the development of enzymatic preparations as
acid-resistant lipases that cause a fast release of free fatty acids i
n the duodenum.