Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.4 (trypsin)
 42,187 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In homogenates and subcellular fractions of pancreatic islets of Wistar rats we could demonstrate three groups of protein degrading enzymes. The proteinases of group 1 are characterized by both trypsin-like and carboxypeptidase B-like specificities with slightly acid pH optima (pH 5.5-6.5) and seem to play important roles in the conversion of proinsulin into insulin. The properties suggest that these enzymes localized in the secretion granule/mitochondria fraction are related to the tissue cathepsins. Group 2 enzymes are thiol-depending proteinases with a pH optimum at 7.0 occuring mainly in the cytosol and to a lesser extent in the fraction of nuclei and cell debris. Group 3 represents the thiol protein oxidoreductase with a pH optimum of 7.0. This enzyme degrading disulfide bonds could also be important in the formation of the disulfide bonds during protein folding after synthesis.
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PMID:Proteolytic and transhydrogenolytic activities in isolated pancreatic islets of rats. 35 9

This work addressed the problem of heterogeneity of immunoreactive insulin (IRI) in human plasma. Subjects with normal glucose tolerance were given 75g of an oral glucose solution, followed in 30 min by an intravenous infusion of 30g of arginine over 30 min. At the end of the infusion blood was withdrawn for analysis. IRI was extracted from plasma of individual subject by immunosorbent columns and was fractionated by gel filtration, disc gel electrophoresis and isoelectric focusing. Human IRI components were identified by molecular size, immunoreactivity with a human proinsulin antibody, sensitivity to trypsin, and by comparison of electrophoretic mobility and isoelectric point with porcine pancreatic products, after suitable correction for electric charge and molecular weight differences. The pattern of IRI heterogeneity was the same among six healthy subjects. Heterogeneity of proinsulin-size IRI in circulation was more marked than that of insulin-size material. Proinsulin and desdipeptide proinsulin were present in approximately equal amounts accompanied by minor amounts of split proinsulin and monodesamido-desdipeptide proinsulin. Insulin-size IRI contained over 80% insulin. Minor amounts of monodesamidoinsulin and diarginylinsulin were observed in some cases. The types of IRI components observed in plasma are evidence in support of a physiologic role of trypsin-and carboxypeptidase B-like enzymes in the conversion of proinsulin to insulin. Moreover, this study provides a base line for investigation of abnormalities in proinsulin-to-insulin conversion that may be associated with certain pathologic states.
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PMID:Characterization of proinsulin-insulin intermediates in human plasma. 35 97

Plasma trypsin concentrations were measured in 403 fasting diabetics and 106 healthy controls. Basal trypsin concentrations in the normal subjects were 88 +/- 6 ng/ml (mean +/- S.E.M.). Mean plasma trypsin concentrations in diabetics treated with diet alone (n = 74) were 45 +/- 2 ng/ml, while in a group of young (less than 35 years, n = 88) insulin-dependent diabetics, they were very low at 29 +/- 2 ng/ml and these levels were inversely related to insulin dosage. The findings may help in the understanding of the pathophysiological changes in the exocrine pancreas in the diabetic state and may also shed some light on the physiological interrelationship between the endocrine and exocrine pancreas.
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PMID:Hypotrypsinaemia in diabetes mellitus. 38 75

A pancreatic endopeptidase localized to the beta-cells of the pancreas by immunohistochemical techniques has been purified to homogeneity by following its functional and antigenic characteristics as a glandular kallikrein (EC 3.4.21.8). The enzyme gave a single stained band on alkaline disc gel electrophoresis which corresponded in location with the kinin-generating activity eluted from a replicate gel, was of 54,000 molecular weight by gel filtration, was devoid of caseinolytic activity, elicited a monospecific antiserum in a rabbit, and gave a line of complete identity with a single constituent in pancreatic extract, crude urine, and purified urokallikrein when analyzed with monospecific antibody to urokallikrein. The pancreatic glandular kallikrein generated three cleavage products of increasing anodal mobility from bovine and porcine proinsulin, and the presence of pancreatic kininase or bovine carboxypeptidase B increased the quantity of these products. Although the conversion products did not correspond to diarginyl- and monoarginylinsulin, the product of intermediate mobility was also obtained when proinsulin was treated with a low concentration of trypsin in the presence of kininase. The most rapidly migrating product did correspond to desalanylinsulin in the reference standard. Kininase alone had no action on proinsulin, and aprotinin prevented cleavage by kallikrein alone or in combination with kininase. Although the chemical structure of the proinsulin cleavage products has not been established, human pancreatic kallikrein is considered a putative activator of proinsulin because of its location in the beta-cell, its preferential action on proinsulin and kininogen as compared to azocasein, and its capacity to generate insulin intermediate products that are further modified by human pancreatic kininase or bovine carboxypeptidase B.
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PMID:Sequential cleavage of proinsulin by human pancreatic kallikrein and a human pancreatic kininase. 38 42

We have studied the effects of the serum from a patient with an unusual form of diabetic syndrome with extreme insulin resistance on the metabolism of rat adipocytes in vitro. This serum and IgG fractions from it inhibited the [125I]insulin binding to isolated adipocytes and stimulated the 2-deoxyglucose uptake, glucose oxidation, and the incorporation of amino acids into protein. In addition, these fractions inhibited the lipolysis induced by beta 1-24 ACTH in isolated adipocytes. The insulin-like effects of this serum and the effects of insulin were not additive at their maximal concentrations. The inhibition of [125I]insulin binding was due to a decrease in receptor affinity rather than to a change in receptor number by Scatchard plot analysis. Both the inhibition of insulin binding and the insulin-like effects on rat adipocytes were neutralized by antihuman IgG. In addition, these insulin-like effects were abolished by trypsin treatment of adipocytes. These facts suggest that this serum has a circulating antibody directed at or near the insulin receptor itself and that this antibody mimics the insulin effect on rat adipocytes by binding to the insulin receptor in vitro.
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PMID:Effects of antiinsulin receptor autoantibody on the metabolism of rat adipocytes. 40 Jul 15

Incubation of fat cells with insulin increased glycogen synthase I activity without changing total synthase activity. This effect of insulin was dependent upon the particular lot of albumin present in the medium and was abolished by incubating cells with trypsin. Half-maximal activation of glycogen synthase was obtained with 8 microunits/ml of insulin, a concentration very similar to that which half-maximally stimulated 3-O-methylglucose uptake. The basal percentage of phosphorylase a activity was not detectably altered by insulin, although it was decreased by incubating cells with 5 mM glucose. Insulin (50 microunits/ml) markedly opposed actions of epinephrine (0.05 to 10 muM) to increase phosphorylase a activity and decrease glycogen synthase I activity, effects which were observed without glucose. Partial activation of glycogen synthase by insulin was seen after 1 min and complete activation after 4 min. Glucose alone produced a transient increase in synthase I activity. When cells were incubated with insulin plus glucose for 4 min, the increase in the percent synthase I activity was much greater than the additive effects of insulin and glucose alone. This potentiation of the effect of insulin on glucogen synthase I activity depended on the time of incubation with glucose and on the concentration of the hexose. If cells were incubated with cytochalasin B before insulin plus glucose, the effect of glucose was abolished. These results suggest that there are at least two mechanisms by which insulin can increase fat cell glycogen synthase I activity. One requires glucose and activation occurs secondary to an increase in glucose transport; where another mechanism(s) is operative even in the absence of glucose.
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PMID:Activation of rat adipocyte glycogen synthase by insulins. 40 14

The saturable insulin binding is linked to insulin degradation in two important target cells: The hepatocyte and the adipocyte. One of the consequences is that the changes in binding which are observed under various conditions cannot a priori be regarded as caused by either increased number of receptors or increased affinity of the binding site. This observation raises new questions. For instance, could the effect of insulin be mediated by a fragment of the molecule? No evidence which is available for the moment seems to rule out this hypothesis. The findings with insulin analogues, the kinetics of insulin binding and activation and the effect of mild trypsin treatment, would equally well support the hypothesis that the binding itself causes activation of hexose transport and that degradation secondary to binding mediates the activation.
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PMID:[Insulin receptors (author's transl)]. 40 44

A high yield of viable single cells was attained from isolated pancreatic islets of adult rat by the sequential treatment with EDTA and Dispase. The percentage of single cells was consistently higher with EDTA-Dispase in comparison with EDTA-trypsin treatment, being 65.8 +/- 7.9% and 36.0 +/- 5.4% respectively, when more than 90% of total islet cells were viable. Excellent preservation of free islet cells dissociated with EDTA-Dispase was demonstrated morphologically by light and electron microscopy. The secretory response of dissociated B cells to glucose was stabilized earlier with EDTA-Dispase than with EDTA-trypsin treatment. The amount of insulin released into the medium was proportional to the number of cells inoculated, thus permitting the quantitative analysis of B-cell function in vitro.
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PMID:Preparation of single cells from pancreatic islets of adult rat by the use of dispase. 41 Jun 34

The cleavage specificity of a protease from Thermoactinomyces vulgaris (thermitase) was determined by the insulin B-chain and the cleavability of casein and haemoglobin by this enzyme as compared to other proteases (trypsin, chymotrypsin, proteases from Bac. megaterium and cytophages). The most intense splitting effect on the substrates under investigation (insulin B-chain, casein and haemoglobin) is exerted by thermitase, i. e., the unspecificity of this enzyme is especially marked.
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PMID:[Substrate specificity of a protease from Thermoactinomyces vulgaris]. 46 Mar 96

The possible role of calcium in human bile during the biliary stimulated exocrine pancreatic secretion was investigated in 15 healthy volunteers. Total outputs of trypsin, bicarbonate, bilirubin and volume in the duodenal juice and serum gastrin were measured during a continuous intravenous infusion of secretion (0.5 CHR U/kg/h) for 40 min. The same parameters were determined after a single intraduodenal dose of Ca++ (20 ml 13,5, 135 or 270 mval/l, n = 5 for each dose) and compared with aequivalent intraduodenal dose of Na+ and an intravenous dose of secretion/cholecystokinin (1 CHR and IDU U/kg). Low calcium (13,5 mval/l) had no effect on the output of pancreatic enzymes and bile. However the higher doses led to a significant increases of the outputs of trypsin and bilirubin, which was about 75% of the enhancement seen with secretin/cholecystokinin in the dose used. Serumgastrin secretion was significantly increased only after the higher calcium doses.--Serum insulin in peripheral venous blood venous blood was unchanged after duodenal application of 20 ml 270 mval/l calcium (n = 5). From these data one has to conclude that the Ca++-content of bile has no stimulatory effect on the exocrine pancreas and on serum gastrin and insulin.
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PMID:[Exocrine pancreatic secretion, gastrin and insulin in men by intraduodenal bolus injection of calcium (author's transl)]. 46 72


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