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)

The degradation of insulin by insulin protease and glutathion-insulin transhydrogenase (glutathioneproteindisulphide oxidoreductase--EC 1.8.4.2, GIT) was measured in rat liver either after replacing food and water by 15% glucose solution, or after daily insulin administration 8 U daily for 3 days or after fasting. The breakdown of radioiodinated insulin was followed by measuring the increase of TCA soluble radioactivity during incubation of cell fractions with 125I insulin at 37 degrees C. The highest GIT activity was observed in liver microsomes of rats after glucose feeding and after insulin administration, whereas enzyme activity of fasted animals did not essentially differ from corresponding values of normally fed controls. The insulin protease in cytosol of liver cells remained unchanged after these procedures. The important role of GIT in insulin degradation seems to be conclusively demonstrated.
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PMID:Effect of insulin and glucose on the activity of insulin-degrading enzymes in rat liver. 30 91

It was previously proposed (Varandani, P. T., Proc Natl Acad Sci 69:1681, 1972) that insulin is first degraded by rat liver homogenates in an enzyme-catalyzed reductive process by microsomal glutathione-insulin transhydrogenase before being proteolytically cleaved by the cytosolic enzyme activity designated insulin protease. This study was, however, carried out with concentrations of the hormone 10,000 times the maximal concentration seen in peripheral blood. In the present study, physiological levels of insulin (approximately 0.1 nM) and concentrations of reduced and oxidized glutathione approximating the reductive potentials of normal liver were used. Rates of degradation by separable particulate and soluble components of the homogenate were determined by following enzymatic conversion of [125I]-iodoinsulin to the trichloroacetic acid-solube form. Assessment of the mode of degradation was determined by gel filtration on Sephadex G-50 in the presence of 1 M acetic acid-6M urea. From these studies it was seen that 1) insulin is reduced at a very significant rate nonenzymatically; 2) during short periods of incubation (30 sec) where no significant hormone is reduced nonenzymatically, the rate of cleavage by the insulin protease present in the cytosol is extremely high and the microsomal GIT activity is negligible; and 3) insulin destruction noted in isolated liver cells and perfused liver is most probably due to the insulin protease activity of the cytosol.
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PMID:The importance of proteolysis as the initial step of insulin degradation in rat liver homogenates. 44 84

The kidney plays a pivotal role in the clearance and degradation of circulating insulin and is also an important site of insulin action. The kidney clears insulin via two distinct routes. The first route entails glomerular filtration and subsequent luminal reabsorption of insulin by proximal tubular cells by means of endocytosis. The second involves diffusion of insulin from peritubular capillaries and subsequent binding of insulin to the contraluminal membranes of tubular cells, especially those lining the distal half of the nephron. Insulin delivered to the latter sites stimulates several important processes, including reabsorption of sodium, phosphate, and glucose. In contrast, insulin delivered to proximal tubular cells is degraded to oligopeptides and amino-acids by one of two poorly delineated enzymatic pathways. One pathway probably involves the sequential action of insulin protease and either GIT or non-specific proteases; the other probably involves the sequential action of GIT and lysosomal proteases. The products of insulin degradation are reabsorbed into the peritubular capillaries, apparently via simple diffusion. Impairment of the renal clearance of insulin prolongs the half-life of circulating insulin by a number of mechanisms and often results in a decrease in the insulin requirement of diabetic patients. Much needs to be learned about these metabolic events at the subcellular level and how they are affected by disease states. Owing to the heterogeneity of cell types within the kidney and to their anatomical and functional polarity, investigation of these areas will be challenging indeed.
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PMID:The renal metabolism of insulin. 638 40