Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.24.56 (insulin-degrading enzyme)
 737 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

RIN-m cells, cultured from a rat insulinoma, not only bind and secrete but also degrade insulin (Diabetes 1982; 31:521-31). The insulin-degrading activity resides in the cytosol and is similar to the insulin-specific proteases previously described in muscle and other tissues. It has an apparent Km of 0.15 microM for porcine insulin in crude cell-free extracts, a competitive inhibition constant for proinsulin that is close to the Km, and a lower but measurable affinity for glucagon. The enzyme is inactive at pHs below 6.0, indicating that it is not lysosomal, is completely inhibited by N-ethylmaleimide, and exhibits apparent competitive inhibition constants (microM) for the following peptides: desoctapeptide insulin, 0.043; guinea pig insulin, 0.048; proinsulin, 0.64; insulin B-chain, 1.17; glucagon, 7.0; and cyclic somatostatin, 8.6. Highly active insulin-degrading activity was found using cell suspensions of 22 cloned and 8 subcloned cell lines derived from RIN-m as well as 11 other continuous cell lines derived from a variety of nonislet tissues of rat, mouse, and human origin. Homogenates of the original rat islet tumor and cytosol of normal rat islets also contained insulin-degrading activity. Although insulin protease is present in a variety of tissues, it may have an additional regulatory function in cells that are actively synthesizing, storing, and secreting insulin.
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PMID:Cytosolic insulin-degrading activity in islet-derived tumor cell lines and in normal rat islets. 298 50

A method has been described for the direct measurement of proinsulin in human plasma. The method makes use of an insulin-degrading enzyme designated "insulin-specific protease (ISP)", which is obtained from rat skeletal muscle. Under the conditions used, this enzyme rapidly degrades insulin and insulin-like polypeptides to nonimmunoassayable components, whereas proinsulin and proinsulin cleaved at position B(54,55) are not appreciably affected. The incubation of plasma with ISP results in the disappearance of insulin, but not proinsulin, as demonstrated by column chromatography. Immunoassay of the plasma, therefore, before and after incubation, determines the values for the total immunoreactive substance (TIR) and for immunoreactive proinsulin (IRP), respectively. The values obtained for proinsulin levels are reproducible and compare closely with the more complicated column fractionation methods. Proinsulin responses were studied in four normal subjects and one patient with an insulinoma after a glucose load. Fasting proinsulin levels varied widely in the normal subjects, and the levels rose more slowly than TIR levels after glucose. IRP levels in the patient with an insulinoma were very high and fell to normal after removal of the tumor. The ISP method, therefore, appears to be suitable for the direct, accurate, and rapid determination of proinsulin and proinsulin-like materials in human plasma.
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PMID:Direct measurement of proinsulin in human plasma by the use of an insulin-degrading enzyme. 432 76

Amylin (islet amyloid polypeptide) is the chief component of the islet amyloid found in type 2 diabetes, and amylin fibril precursors may be cytotoxic to pancreatic beta-cells. Little is known about the prevention of amylin aggregation. We investigated the role of insulin-degrading enzyme (IDE) in amylin degradation, amyloid deposition, and cytotoxicity in RIN-m5F insulinoma cells. Human (125)I-labeled amylin degradation was inhibited by 46 and 65% with the addition of 100 nmol/l human amylin or insulin, respectively. (125)I-labeled insulin degradation was inhibited with 100 nmol/l human amylin, rat amylin, and insulin (by 50, 50, and 73%, respectively). The IDE inhibitor bacitracin inhibited amylin degradation by 78% and insulin degradation by 100%. Amyloid staining by Congo red fluorescence was detectable at 100 nmol/l amylin and was pronounced at 1,000 nmol/l amylin treatment for 48 h. Bacitracin treatment markedly increased staining at all amylin concentrations. Bacitracin with amylin caused a dramatic decrease in cell viability compared with amylin alone (68 and 25%, respectively, at 10 nmol/l amylin). In summary, RIN-m5F cells degraded both amylin and insulin through a common proteolytic pathway. IDE inhibition by bacitracin impaired amylin degradation, increased amyloid formation, and increased amylin-induced cytotoxicity, suggesting a role for IDE in amylin clearance and the prevention of amylin aggregation.
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PMID:An insulin-degrading enzyme inhibitor decreases amylin degradation, increases amylin-induced cytotoxicity, and increases amyloid formation in insulinoma cell cultures. 1294 71