Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Studies are presented dealing with the effect on the exocrine and endocrine pancreas of long-term oral trypsin inhibitor administration to alloxan diabetic rats. Three categories of rats were used: a) normal rats, b) alloxan diabetic rats, and c) alloxan diabetic rats treated with the trypsin inhibitor. 1. The concentration of amylase in both pancreas and intestinal contents were markedly decreased in alloxan diabetic rats as compared with normal rats, whereas the concentrations of lipase and trypsin(ogen) were practically unaffected by the diabetic state. 2. Trypsin inhibitor treatment of diabetic rats enhanced the concentrations of both amylase, trypsin(ogen), and lipase in pancreas and intestinal contents when compared with untreated diabetic controls. 3. Alloxan diabetic rats treated with trypsin inhibitor displayed an increased weight gain, increased pancreatic weight, and increased pancreatic protein concentration as compared with the untreated diabetic controls. 4. Alloxan diabetic rats treated for 3 or 5 weeks with the trypsin inhibitor were found to have decreased basal blood glucose levels and an increased plasma insulin: blood glucose ratio as compared to the untreated diabetic controls. 5. There was no apparent difference in the glucose elimination rate after I.V. glucose loads in diabetic rats given trypsin inhibitor and their diabetic controls. However, the insulin secretory response to the glucose stimulus was slightly improved in the trypsin inhibitor group. 6. Alloxan diabetic rats treated with trypsin inhibitor had an increased total pancreatic insulin content compared with their diabetic controls. It is concluded that long-term daily treatment with oral trypsin inhibitor in alloxan diabetic rats increased enzyme production and secretion in the exocrine pancreas, and produced an improvement of the diabetic condition of the animals. This improvement might partly be due to an increased pancreatic content and secretion of insulin.
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PMID:Oral trypsin-inhibitor-induced improvement of the exocrine and endocrine pancreatic functions in alloxan diabetic rats. 77 3

The present study revealed that glucose-induced insulin secretion was significantly inhibited by perfusion with trypsin (10 mug/ml) in the isolated rat pancreas perfusion. However, when trypsin was interposed during perfusion of 16.6 mM glucose, glucose-induced insulin secretion was not suppressed during trypsin infusion. The insulin level was significantly lower in the trypsin treated animals than in the control after completion of trypsin infusion. The results suggest that trypsin does not attack the glucorecoptor bound with glucose but attacks the free glucoreceptor. Interestingly a biphasic pattern of glucose-induced insulin secretion disappeared by the pretreatment with trypsin. The possibility was suggested that tyrpsin prevented the initial binding of glucose to the B-cell.
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PMID:Effects of trypsin on glucose-induced insulin secretion from the perfused rat pancreas. 77 37

Trypsin-like and carboxypeptidase B-like proteinases are believed to play important roles in the conversion of proinsulin into insulin as well as in the intracellular processing of a variety of other precursor forms. To facilitate the study of these enzymes we have developed sensitive methods for their detection in tissue preparations and incubation media. Studies with rat islet homogenates indicate the presence of both trypsin-like and carboxypeptidase B-like activities with slightly acidic pH optima. The trypsin-like activity was activated by thiols and inhibited by several thiol reagents but the carboxypeptidase was inhibited only by chelating agents. These properties suggest that these enzymes are related to the tissue cathepsins. Additional experimental approaches to the problems of positively identifying and localizing converting enzymes at the subcellular level are briefly discussed.
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PMID:Carboxypeptidase B-like and trypsin-like activities in isolated rat pancreatic islets. 82 May 28

Autoantibodies to the insulin receptor have been detected in the sera of several patients with the Type B syndrome of insulin resistance and acanthosis nigricans. In this study we have used three of these sera (B-1, B-2, and B-3) as probes of the insulin receptor in isolated rat adipocytes. Preincubation of adipocytes with each of the three sera resulted in an inhibition of subsequent [(125)I]insulin binding. 50% inhibition of binding occurred with serum dilutions of 1:5 to 1:7,500. As in our previous studies with other tissues, Scatchard analysis of the insulin-binding data was curvilinear consistent with negative cooperativity. Computer analysis suggested that in each case the inhibition of binding was due to a decrease in receptor affinity rather than a change in available receptor number. In addition to the effects on insulin binding, adipocytes pretreated with antireceptor sera also showed alterations in biological responses. All three sera produced some stimulation of basal glucose oxidation. With serum B-3, maximal stimulation of glucose oxidation occurred at a serum concentration that inhibited binding by only 10-15%, whereas with serum B-2 the dilution curves for inhibition of binding and stimulation of glucose oxidation were superimposable. Serum B-1 behaved as a partial agonist; that is, it inhibited binding more effectively than it stimulated glucose oxidation. Cells pretreated with this serum in a concentration which inhibited binding by 80% also showed a five-fold shift to the right in the dose response of insulin-stimulated glucose oxidation, whereas spermine-stimulated glucose oxidation was unaffected. Serum B-2, which contained the highest titer of antireceptor antibodies, also stimulated 2-deoxy-glucose transport, as well as glucose incorporation into lipid and glycogen. Both the ability of the serum to inhibit binding and stimulate glucose utilization were enriched in purified immunoglobulin fractions and retained in the F(ab')(2) fragment of the IgG. In addition, the bioactivity was blocked by antihuman IgG but not by anti-insulin antibodies. Enzymatic digestion of adipocytes with trypsin resulted in a complete loss of insulin-stimulated bioactivity of serum B-3, but had only minor effects on the glucose oxidation produced by serum B-1 or B-2.These data suggest that the antibodies present in these three sera bind to different determinants on the insulin receptor. Thus, these antibodies may be useful probes of receptor structure and function.
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PMID:Effects of autoantibodies to the insulin receptor on isolated adipocytes. Studies of insulin binding and insulin action. 90 53

The effect of long-term oral trypsin inhibitor administration on blood glucose, plasma insulin, liver, and muscle glycogen and glucose utilization in vitro by peripheral tissues in normal and diabetic rats was studied. In normal rats the glycogen levels in liver and muscle were increased after 3 weeks of treatment. Glucose oxidation (14CO2-production) was augmented in muscle after 3 and 8 weeks and in liver after 3 weeks. An increased 14C-incorporation into glycogen from 14C-glucose and increased glycogen concentration after incubation were found in muscle after 3 weeks. In diabetic rats the basal blood glucose was decreased after 3 and 5 weeks of treatment, and the basal plasma insulin:blood glucose ratio increased after 5 weeks. The glycogen levels were increased after 3 and 5 weeks in liver. No effect on glucose oxidation (14CO2-production) in muscle was found. The 14C-incorporation into glycogen and the total glycogen content, however, was increased in muscle after both 3 and 5 weeks. Incubation of muscle tissue with serum from normal or diabetic rats treated with oral trypsin inhibitor for 3 and 5 weeks respectively had no apparent acute effects on the glucose metabolism. It is suggested that the observed action of oral trypsin inhibitors on glucose metabolism in peripheral tissues is mediated by one or more unknown gastrointestinal factor(s).
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PMID:Carbohydrate metabolism in normal and diabetic rats following long-term oral trypsin inhibitor administration. 93 97

The enzymic hydrolysis of some proteins (insulin-B-chain-S-sulfonate, S-aminoethylated lysozyme, bovine serum albumin) by immobilized peptidolytic enzymes is reported. Sepharose-bound pronase, trypsin and a protease from Thermoactinomyces sp. (MP), the latter both cross linked by glutaric dialdehyde and an exopeptidase mixture containing Sepharose-bound leucine aminopeptidase, carboxypeptidase A and a crude preparation of prolidase were used. After enzymic hydrolysis nearly all amino acids, except proline, were recovered in a 100% yield compared to the value of an acid reference hydrolysate. Tryptophan and methionine, which are partially destroyed by acid hydrolysis in the presence of oxygen could be recovered completely.
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PMID:[Protein hydrolysis by immobilized enzymes]. 98 21

Insulin, a mitogen for cultured chick embryo fibroblasts (Temin, H.M. (1968) Cancer 3, 771-787), has been employed to characterize the effects of mitogen/cell membrane interactions as it relates to growth. The specific binding of 125I-insulin to substratum-attached cells is time- and temperature dependent and is optimum at a pH of 7.0. Fetal calf and chicken sera, somatomedin "A/C mixed," and desalanine or native porcine insulin compete with 125I-insulin for membrane-binding sites. Proinsulin, although competing less effectively than native insulin for binding, is more effective than desoctapeptide insulin. Unrelated polypeptide hormones do not compete for 125I-insulin binding. The lowest concentration of insulin at which specific binding is detected is 0.1 nM. Scatchard plot analysis of the binding data indicates that there are two types of binding sites in confluent cultures of fibroblasts: one of high affinity (K1 = 2 to 6 X 10(8) M-1) and low capacity, the other of low affinity (K2 = 0.8 to 3.0 X 10(7) M-1) and high capacity. Approximately 1.9 and 7.1 X 10(3) molecules of insulin are bound at each site, respectively. A 10-min incubation at 24 degrees of the fibroblasts with 10 mug/ml of trypsin causes a 2-fold stimulation of specific 125I-insulin binding and a similar 2-fold increase in insulin-stimulated 2-deoxy-D-glucose uptake and thymidine incorporation. Neuraminidase treatment also produces a 37% increase in specific 125I-insulin binding but treatment with alpha-chymotrypsin or phospholipase C are without significant effect. The results of this and additional experiments support the hypothesis that trypsin treatment of chick embryo fibroblasts leads to an unmasking of 125I-insulin binding sites. Serum starvation of fibroblasts for 12 or 24 h produces a 2.5- to 5-fold increase in specific 125I-insulin binding. This increase is the result of an increase in the number of hormone-binding sites from 9 X 10(3) to 6 X 10(4) per cell which are predominantly of the low affinity type. There is no change in the affinity constants. The presence of camptothecin, or cordycepin, or cycloheximide in the incubation medium completely blocks the increase in number of 125I-insulin-binding sites resulting from serum starvation. The addition of native insulin to the medium of serum-starved cultures also blocks this increase. The magnitude of insulin-stimulated 2-deoxy-D-glucose uptake and thymidine incorporation correlates with the levels of occupancy of the low affinity 125I-insulin-binding sites in untreated fibroblasts. In fibroblasts cultured in the absence of serum, the marked increase in insulin-stimulated 2-deoxy-D-glucose uptake and thymidine incorporation parallels the increase in number of mitogen receptors. The concentration of insulin that produces a half-maximum stimulation of thymidine incorporation is calculated to be 5 X 10(-8) M. At this concentration of insulin, 42% of the receptor sites are occupied.
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PMID:Mitogen receptors in chick embryo fibroblasts. Kinetics, specificity, unmasking, and synthesis of 125I-insulin binding sites. 98 22

Analysis of the plasma from a totally pancreatectomized patient, with antiserum 30 K, has demonstrated basal glucagon immunoreactivity (GIR) levels in the normal range (80-110 pg/ml). Neither i. v. arginine nor oral glucose affected these GIR values, thus indicating the absence of functioning pancreatic or gastrointestinal A-cells. Furthermore, filtration of whole plasma on Bio Gel P-30 showed no GIR in the 3500 MW elution volume. GIR was found to be distributed in two peaks. One peak eluted in the protein region, similarly to "big plasma glucagon" (BPG), and the second peak appeared after the glucagon-I125 marker. The protein-sized moiety was not absorbable by charcoal, and on Sephadex G-100 it eluted within the globulin region. When subjected to trypsin treatment, it yielded smaller GIR fractions. According to these criteria, it can be assumed that this component is identical to BPG. Therefore, an extrapancreatic source for BPG is suggested. On the other hand, the presence of fasting hyperglycaemia in this patient indicates that insulin deficiency by itself suffices to raise blood sugar to diabetic levels.
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PMID:Plasma glucagon immunoreactivity in a totally pancreatectomized patient. 100 50

1. Trypsin-treated human and rat fat cells were obtained by digestion of adipose tissue with collagenase plus trypsin and their lipolytic response to insulin, catecholamines and dibutyryl cyclic AMP were compared with the lipolytic response of human and rat fat cells isolated with collagenase only. 2. In both human and rat fat cells, no significant modification occurred in the intracellular lactate dehydrogenase content and in the basal release of glycerol after trypsination. 3. In rat fat cells, trypsin abolished the antilipolytic effect of insulin but maintained a normal lipolytic response to epinephrine, norepinephrine and isoproterenol. 4. In human fat cells, on the contrary, trypsin failed to modify the antilipolytic effect of insulin, but markedly potentiated the lipolytic response to epinephrine, norepinephrine and isoproterenol. Trypsin also increased the rate of intracellular 3' :5' cyclic AMP accumulation in response to catecholamines. Under these conditions, however, trypsin-treated human fat cells had a normal reponse to the lipolytic agent dibutyryl cyclin AMP. 5. These data suggest that human fat cells differ from the rat ones by the existence in human adipocyte membranes of a trypsin-sensitive component which inhibits the catecholamine induced lipolytic process and which is different from the alpha receptors.
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PMID:Influence of trypsin on lipolysis in human fat cells. Comparison with rat adipocytes. 100 93

Evidence is presented that proglucagon from anglefish islets is a single chain polypeptide with 78 amino acid residues and that the glucagon portion of it is liberated after tryptic cleavage. The most striking characteristic in the conversion of the anglerfish proglucagon to glucagon is that the cleaved peptide bonds display enormous sensitivity toward trypsin. Thus, conversion of the prohormone to glucagon occurs very rapidly within 3-10 min with a 1:500-1:1000 molar ratio of enzyme to substrate. Further, trypic cleavage of the anglerfish glucagon requires higher concentrations of trypsin (molar ratio 1:25 enzyme to substrate) and longer incubation time. The behavior of proglucagon and glucagon toward trypsin shows striking similarities with the tryptic conversion of anglerfish proinsulin to insulin.
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PMID:Isolation and partial characterization of anglefish proglucagon. 109 38


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