Role of lipase in the regulation of upper gastrointestinal function in humans.
The role of lipase in the regulation of upper gastrointestinal function is poorly understood. We studied the effect of orlistat, a new, potent, and highly specific lipase inhibitor, on gastric emptying, cholecystokinin (CCK) release, and pancreaticobiliary secretion. Three groups of studies were performed in nine healthy volunteers, using the double-indicator technique with a triple-lumen duodenal tube, polyethylene glycol 4000 as a duodenal perfusion marker, and 99mTc-diethylenetriamine pentaacetic acid as a meal marker. Gastric emptying, pancreaticobiliary output, and postprandial plasma CCK levels were measured after ingestion of the following isocaloric 500-ml liquid meals with or without 200 mg orlistat: 1) a pure fat meal (10% Intralipid), 2) a meal containing free fatty acids, or 3) an albumin-glucose meal. All experiments were performed in a randomized, placebo-controlled, crossover design. Orlistat markedly inhibited lipase activity in all three experiments. Orlistat given with the fat meal reduced CCK release and output of lipase, trypsin, and bilirubin and accelerated the rate of gastric emptying (P < 0.05). After ingestion of the free fatty acid or albumin-glucose meal, orlistat had no significant effect on any of these parameters. We conclude that lipase plays an important, nutrient-specific role in the regulation of gastric emptying and pancreaticobiliary secretion after ingestion of fatty meals in humans.
Schwizer
W
W
Department of Gastroenterology, University Hospital, Zurich, Switzerland.
Asal
K
K
Kreiss
C
C
Mettraux
C
C
Borovicka
J
J
Rémy
B
B
Güzelhan
C
C
Hartmann
D
D
Fried
M
M
D000328:Adult; D001663:Bilirubin / Q000097:blood / Q000378:metabolism; D002766:Cholecystokinin / Q000097:blood / Q000378:metabolism*; D004386:Duodenum / Q000187:drug effects / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005217:Fat Emulsions, Intravenous; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005704:Gallbladder / Q000187:drug effects / Q000378:metabolism; D005746:Gastric Emptying / Q000187:drug effects*; D006801:Humans; D007783:Lactones / Q000494:pharmacology*; D008049:Lipase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008297:Male; D000077403:Orlistat; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism; D012016:Reference Values; D016284:Technetium Tc 99m Pentetate; D013997:Time Factors; D014357:Trypsin / Q000378:metabolism
D004791:Enzyme Inhibitors; D005217:Fat Emulsions, Intravenous; D005230:Fatty Acids, Nonesterified; D007783:Lactones; D002766:Cholecystokinin; D000077403:Orlistat; D008049:Lipase; D014357:Trypsin; D001663:Bilirubin; D016284:Technetium Tc 99m Pentetate