1998
DOI: 10.1111/j.2042-7158.1998.tb06192.x
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Investigation into the Presence of Insulin-degrading Enzyme in Cultured Type I1 Alveolar Cells and the Effects of Enzyme Inhibitors on Pulmonary Bioavailability of Insulin in Rats

Abstract: The purpose of this study was to investigate the role of insulin-degrading enzyme (IDE, EC 3.4.22.11) in insulin degradation in alveolar epithelium. The primary culture of isolated rat type-II pneumocytes was used for the in-vitro characterization of IDE. Insulin was then administered intratracheally with various inhibitors to assess the improvement in its pulmonary bioavailability. In cultured type-II pneumocytes, the cytosolic insulin-degrading activity contributed 81% of total insulin degradation, reached a… Show more

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Cited by 16 publications
(6 citation statements)
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“…This might seem to contradict what has been published regarding insulin absorption enhancement in presence of protease inhibitors (5,28); however, the inhibitor cocktail composition in our study, which mainly protected against cytosolic and lysosomal proteases, was different from reagents used in other studies (5,9,28) and might not have had the same protective activity against insulin degradation by aminopeptidase present on cell membrane surface. These results may indicate a partial rerouting of insulin transport through the transcellular pathway, exposing it to degradation by lysosomal proteases or cytosolic insulin degrading enzymes known to be present in cultured type II alveolar cells (29). Regardless of the high degradation, this transcellular pathway can maintain the amount of insulin transport at a higher level than that in cells incubated with SM.…”
Section: Discussionmentioning
confidence: 91%
“…This might seem to contradict what has been published regarding insulin absorption enhancement in presence of protease inhibitors (5,28); however, the inhibitor cocktail composition in our study, which mainly protected against cytosolic and lysosomal proteases, was different from reagents used in other studies (5,9,28) and might not have had the same protective activity against insulin degradation by aminopeptidase present on cell membrane surface. These results may indicate a partial rerouting of insulin transport through the transcellular pathway, exposing it to degradation by lysosomal proteases or cytosolic insulin degrading enzymes known to be present in cultured type II alveolar cells (29). Regardless of the high degradation, this transcellular pathway can maintain the amount of insulin transport at a higher level than that in cells incubated with SM.…”
Section: Discussionmentioning
confidence: 91%
“…Determination of drug concentrations in tissue may also provide information on drug metabolism in the lung, such as those reported for insulin [115].…”
Section: Determination Of Local and Systemic Drug Concentrationsmentioning
confidence: 99%
“…Two enzymes that degrade insulin have been extensively studied; glutathione-insulin transhydrogenase, also called protein disulfide isomerase, interchanges the disulfide bonds in the insulin molecule and insulin-degrading enzyme (IDE), insulinase or insulysin that proteolytically clips insulin (6). IDE has been identified as the major protease responsible for the degradation of insulin by intestinal cells and alveolar epithelium (6)(7)(8).…”
Section: Introductionmentioning
confidence: 99%
“…Cases of extreme subcutaneous insulin resistance (SIR) are rare and were first reported in the 1970s by Schneider (1) and Paulsen (2) (6)(7)(8). (5,7,9,10 …”
Section: Introductionmentioning
confidence: 99%