title: Susceptibility of insulin to proteolysis in rat lung homogenate and its protection from proteolysis by various protease inhibitors.
abstract: The objective of this study was to determine the stability of insulin in rat lung homogenate and to confirm the effectiveness of various protease inhibitors for insulin delivery from the lung. The stability of insulin in rat lung homogenate was compared with that in the small intestine. Insulin was rapidly degraded in lung homogenate similarly to degradation in the small intestinal homogenate. The effects of various protease inhibitors on the degradation of insulin were studied in the lung. Protease inhibitors such as Na-glycocholate (Na-GC; 10 mM), aprotinin (10 mg/ml), soybean trypsin inhibitor (STI; 10 mg/ml) and bacitracin (20 mM) effectively reduced insulin degradation in lung homogenate. The rank order of effectiveness for decreasing the insulin hydrolysis in lung homogenate was bacitracin > aprotinin > STI > Na-GC. In addition, a slight correlation was observed between the in situ pulmonary absorption of insulin and its stability in vitro in the lung homogenate in the presence of various protease inhibitors. These findings suggest that the coadministration of protease inhibitors would be useful for improving the stability of insulin in the lung.
authors.affiliation: Department of Biopharmaceutics, Kyoto Pharmaceutical University, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Fukuda
authors.forename: T
authors.initials: T
authors.lastname: Tsuji
authors.forename: T
authors.initials: T
authors.lastname: Fujita
authors.forename: A
authors.initials: A
authors.lastname: Yamamoto
authors.forename: S
authors.initials: S
authors.lastname: Muranishi
mesh_terms: D000042:Absorption; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D010450:Endopeptidases / Q000378:metabolism; D006207:Half-Life; D006868:Hydrolysis; D066298:In Vitro Techniques; D007328:Insulin / Q000032:analysis / Q000378:metabolism*; D007421:Intestine, Small / Q000187:drug effects / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D011480:Protease Inhibitors / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D007328:Insulin; D011480:Protease Inhibitors; D010450:Endopeptidases