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Abstract The role of lipase in the regulation of upper gastrointestinal functions and its nutrient specificity is poorly understood. We therefore studied the effect of tetrahydrolipstatin (THL) - a highly specific and potent lipase blocker _ on gastric emptying and pancreatobiliary secretions after a) a pure fat meal (Intralipid(R) 10%), b) a meal containing only free fatty acids (corresponding to the free acids composition of Intralipid), and c) an albumin/glucose meal (10 g% albumin + ]2.5 g% glucose). Nine healthy male volunteers were examined using a triple-lumen tube in the duodenum and the double indicator technique; PEG as a duodenal flow marker, and 99mTc_DTPA as a meal marker. The test meals (500 ml, 500 kcal) were instilled intragastrically with and without 200 mg THL, in a randomized order in two different days at least one week apart. Plasma CCK levels, gastric emptying rates, and outputs of lipase, trypsin, and bilirubin were measured. We found that THL given with a pure fat meal lowered CCK release and accelerated gastric emptying rates while diminishing outputs of pancreato¬biliary secretions. On the other hand, THL given with fat-free meals (albu¬min/glucose) and meals containing only free fatty acids, while potentially |