In vitro and in vivo experiments were undertaken to evaluate enzyme-replacement therapy with an acid stable lipase preparation in pancreatic lipase insufficiency. Utilizing an emulsion of [1-14C] trioleylglycerol, partially purified rabbit gastric lipase exhibited a maximal specific activity of 6.45 μmoles FFA/h, a Km of 80 mM, an optimal peak activities at pH 4.86 and 5.48, and stability in acidic medium. Although preferential lipolysis of medium chain fatty acid ester bonds was evidenced by experiments with a commercial formula (SimilacR) containing 28% MCT (C6-C8-C10-C12), the gastric lipase preparation also displayed ability to split the long chain fatty acid ester bonds in a fine emulsion of triglycerides for IV use (IntralipidR). Triacylglycerol hydrolysis was enhanced either by 4 mM Na-taurocholate or 4 mM Na-glycocholate, and remained unchanged following the addition of these bile salts at 8 mM. These in vitro findings suggested that the gastric lipase preparation was biologically active under the conditions prevailing in the stomach and in the upper small intestine. To investigate its in vivo lipolytic activity exogenous rabbit gastric lipase was added to the stomach of rats with ligated pylorus and oesophagus. With long-chain triacylglycerols as substrate, a 40% increase of ester bond cleavage occurred during 1 h of intragastric incubation, relative to rats from which exogenous enzymes were excluded. Similarly, a level of 40% hydrolysis was reached into the intestine of rats with a diversion of pancreatobiliary secretions. Our studies clearly indicate that hydrolysis of dietary fat may be initiated into the stomach by exogenous gastric lipase preparation and may continue in the upper small intestine. On the basis of these findings, studies in humans with this enzyme preparation appear warranted to define its role in the management of patients with exocrine pancreatic insufficiency who do not respond satisfactorily to currently available enzyme preparations.
- diversion of pancreatobiliary secretions
- Gastric lipase
ASJC Scopus subject areas
- Endocrinology, Diabetes and Metabolism
- Nutrition and Dietetics