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)

Forty-nine patients with tropical calcific pancreatitis (TCP), 51 insulin-dependent diabetics (IDDMs), 87 non-insulin-dependent diabetics (NID-DMs), and 66 nondiabetic controls were studied to evaluate their exocrine pancreatic function by measurement of serum immunoreactive trypsin (IRT, normal for white caucasians from the U.K. of 140-414 micrograms/L), pancreatic isoamylase (PIA, normal of 35-125 U/L), and fecal chymotrypsin (FCT, normal of greater than 6.6 u/g). The majority of patients were studied within 1 year of diagnosis. TCP subjects included 7 nondiabetics, 6 with impaired glucose tolerance (IGT-TCP), and 36 diabetics [fibrocalculous pancreatic diabetes (FCPD)]. There was evidence of active pancreatitis (IRT greater than 800 micrograms/L) and partial preservation of function in nondiabetic TCP subjects [median IRT of 220 micrograms/L (range of 102-1,360 micrograms/L), FCT of 2.2 u/g (range 0.7-12.8 u/g)] and also in IGT-TCP subjects [IRT of 370 micrograms/L (range of 30-1,360 micrograms/L), FCT of 4.2 u/g (range of 1-38 u/g)]. FCPDs showed severely diminished exocrine function [IRT of 50 micrograms/L (range of 0-184 micrograms/L), FCT of 0.23 u/g (range of 0-10.4 u/g)]; none showed IRT greater than 800 micrograms/L. IDDMs and NIDDMs also showed diminished exocrine pancreatic function in approximately 30 and approximately 10%, respectively. Controls showed a wide range of IRT and FCT concentrations; IRT concentrations tended to be higher than those reported in white Caucasians from the U.K. Three controls, one IDDM, and two NIDDMs showed "pancreatic" IRT concentrations in the absence of symptoms. PIA concentrations were diminished in FCPD but were similar in IDDM and NIDDM subjects compared to controls.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Exocrine pancreatic function (serum immunoreactive trypsin, fecal chymotrypsin, and pancreatic isoamylase) in Indian diabetics. 228 Oct 79

A radioimmunoassay was performed for direct measurement of urinary active and trypsin-activatable inactive kallikreins excretion in 34 patients with Type II diabetes mellitus. (1) Diabetics showed slightly low total (inactive plus active) kallikrein excretion, normal inactive kallikrein excretion and significantly low active kallikrein excretion and active-to-total kallikrein ratio. (2) Total kallikrein excretion was normal in normotensive diabetics and hypertensive diabetics without nephropathy, low in hypertensive diabetics with nephropathy. Active kallikrein excretion and active-to-total kallikrein ratio in hypertensive diabetics were remarkably low regardless of nephropathy. (3) Para amino hippurate clearance correlated with total kallikrein excretion in normal subjects and, with active kallikrein excretion and active-to-total kallikrein ratio in both normal subjects and diabetics, but not with total kallikrein excretion in diabetics. Creatinine clearance did not correlate with total, inactive kallikrein excretions and active-to-total kallikrein ratio. (4) A positive correlation was found between fractional sodium excretion and active kallikrein excretion in normal subjects, but not in diabetics. The results suggest that reduction in ratio of active-to-total kallikrein by renal dysfunction might decrease sodium excretion in diabetics with nephropathy.
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PMID:[Studies on kallikrein activity in diabetic patient with hypertension caused by nephropathy]. 274 99

We have previously shown that the incubation of normal rat adipose tissue with sera from nondialyzed, nondiabetic uremic patients reduces the transport and metabolism of glucose, in the absence and presence of insulin. In this study insulin-stimulated glucose metabolism by normal rat adipocytes was used as a bioassay to identify the resistance activity, assess the effect of chemical modification on it, and the clinical states associated with its production. The resistance activity was trypsin-labile and had an apparent isoelectric point between 6 and 7, but was not retained by either protein A or concanavalin A columns. The insulin resistance activity was decreased by coincubation with the protein synthesis inhibitor, cycloheximide. Purification to greater than 200,000-fold was attained by heating (100 degrees C) uremic serum, subjecting the supernatant to Sephadex G-25 chromatography and subsequent adsorption to DEAE at pH 7.8 and elution at pH 6.5. The partially purified resistance activity was retained within dialysis tubing of 1,000-mol wt cutoff but not within 2,000-mol wt cutoff. Hemodialysis of patients over 1 wk to 18 mo reduced significantly the amount of resistance activity in their sera. The resistance activity, present in most uremic patients, was not found in the sera of individuals with normal renal function but who were either obese, fasted, elderly or had type II diabetes mellitus. Thus, a circulating small molecular weight peptide, unique to uremia, induced insulin resistance by a protein synthesis-dependent mechanism.
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PMID:Characterization and partial purification of a factor from uremic human serum that induces insulin resistance. 388 60

We hypothesized that sera from type 2 diabetic patients with neuropathy contains an autoimmune immunoglobulin that promotes complement-independent, calcium-dependent apoptosis in neuronal cell lines. Neuronal cells were cultured in the presence of complement-inactivated sera obtained from patients with type 2 diabetes with and without neuropathy and healthy adult control patients. Serum from diabetic patients with neuropathy was associated with a significantly greater induction of apoptosis, compared to serum from diabetic patients without neuropathy and controls. In the presence of calcium channel antagonists, induction of apoptosis was reduced by approximately 50%. Pretreatment of neuronal cells with serum from diabetic patients with neuropathy was associated with a significant increase in elevated K+-evoked cytosolic calcium concentration. Serum-induced enhancement in cytosolic calcium and calcium current density was blocked by treatment with trypsin and filtration of the serum using a 100,000-kd molecular weight filter. Treatment with an anti-human IgG antibody was associated with intense fluorescence on the surface of neuronal cells exposed to sera from patients with type 2 diabetes mellitus with neuropathy. We conclude that sera from type 2 diabetic patients with neuropathy contains an autoimmune immunoglobulin that induces complement-independent, calcium-dependent apoptosis in neuronal cells.
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PMID:Serum from patients with type 2 diabetes with neuropathy induces complement-independent, calcium-dependent apoptosis in cultured neuronal cells. 976 38

In a large cohort (no. = 361) of NIDDM probands and their concordant/discordant siblings from no. = 132 families we studied: 1. the levels of plasma prorenin in non affected siblings of NIDDM probands as opposed to normal subjects without family history of diabetes, and 2. whether plasma prorenin raises in parallel to urinary protein loss in NIDDM patients. Prorenin (solid-phase trypsin) and micro-macroalbuminuria (radioimmunoassay) were evaluated. Plasma prorenin was higher in NIDDM probands and siblings than in non NIDDM siblings (37+/-31 vs. 25+/-15 ng/ml/h, p<0.0005) who, in turn, showed higher plasma prorenin than non diabetic controls without family history of diabetes (25+/-15 vs. 17+/-8 ng/ml/h, p<0.005). Plasma prorenin was higher in NIDDM siblings of micro-macroalbuminuric probands than in NIDDM siblings of non micro-macroalbuminuric probands (40+/-26 vs. 29+/-20 ng/ml/h, mean +/- SD, p = 0.0058) whereas no difference was found among non diabetic siblings (24+/-14 vs. 22+/-11 ng/ml/h, NS). Our data confirm that plasma prorenin is elevated in NIDDM patients, and show: 1. that the raise of plasma prorenin in non-NIDDM siblings of a diabetic patient does not depend entirely from the presence of diabetes, and 2. that plasma prorenin in NIDDM probands and their concordant siblings goes along with micro-macroalbuminuria.
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PMID:High plasma prorenin in non diabetic siblings of non insulin-dependent diabetes mellitus patients. 1061 25

The concentration of leukocyte elastase/alpha1-proteinase inhibitor complexes in plasma and polymorphonuclear neutrophil extracts, and plasma trypsin inhibitory capacity were determined in 88 patients with type 2 diabetes and 47 control subjects. Higher values of these variables were found in patients as compared to controls (p < 0.001). The concentration of elastase was higher in obese patients than in lean ones (p < 0.05 for plasma, p < 0.01 for polymorphonuclear leukocytes). Only leukocyte elastase levels were significantly higher in the group with both micro- and macroangiopathy in comparison to the group with microangiopathy (p < 0.01) or macroangiopathy (p < 0.05) alone. Poor short-term glycaemic control was associated with higher elastase concentration in plasma and neutrophils (p < 0.05). The present study demonstrates that measurements of plasma polymorphonuclear neutrophil elastase level can be considered as a marker of development of diabetic angiopathy.
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PMID:Concentration of leukocyte elastase in plasma and polymorphonuclear neutrophil extracts in type 2 diabetes. 1120 90

A group of serine peptidases, the prolyl oligopeptidase family, cannot hydrolyze peptides containing more than about 30 residues. This group is unrelated to the classical trypsin and subtilisin families, and includes dipeptidyl peptidase IV, acylaminoacyl peptidase and oligopeptidase B, in addition to the prototype prolyl oligopeptidase. The recent crystal structure determination of prolyl oligopeptidase (80 kDa) has shown that the enzyme contains a peptidase domain with an alpha/beta hydrolase fold, and its catalytic triad is covered by the central tunnel of an unusual seven-bladed beta-propeller. This domain operates as a gating filter, excluding large, structured peptides from the active site. The binding mode of substrates and the catalytic mechanism differ from that of the classical serine peptidases in several features. The members of the family are important targets of drug design. Prolyl oligopeptidase is involved in amnesia, depression and blood pressure control, dipeptidyl peptidase IV in type 2 diabetes and oligopeptidase B in trypanosomiasis.
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PMID:The prolyl oligopeptidase family. 1191 48

IDE (insulin-degrading enzyme) is a widely expressed zinc-metallopeptidase that has been shown to regulate both cerebral amyloid beta-peptide and plasma insulin levels in vivo. Genetic linkage and allelic association have been reported between the IDE gene locus and both late-onset Alzheimer's disease and Type II diabetes mellitus, suggesting that altered IDE function may contribute to some cases of these highly prevalent disorders. Despite the potentially great importance of this peptidase to health and disease, many fundamental aspects of IDE biology remain unresolved. Here we identify a previously undescribed mitochondrial isoform of IDE generated by translation at an in-frame initiation codon 123 nucleotides upstream of the canonical translation start site, which results in the addition of a 41-amino-acid N-terminal mitochondrial targeting sequence. Fusion of this sequence to the N-terminus of green fluorescent protein directed this normally cytosolic protein to mitochondria, and full-length IDE constructs containing this sequence were also directed to mitochondria, as revealed by immuno-electron microscopy. Endogenous IDE protein was detected in purified mitochondria, where it was protected from digestion by trypsin and migrated at a size consistent with the predicted removal of the N-terminal targeting sequence upon transport into the mitochondrion. Functionally, we provide evidence that IDE can degrade cleaved mitochondrial targeting sequences. Our results identify new mechanisms regulating the subcellular localization of IDE and suggest previously unrecognized roles for IDE within mitochondria.
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PMID:Alternative translation initiation generates a novel isoform of insulin-degrading enzyme targeted to mitochondria. 1528 18

Alpha-1-antitrypsin (AAT) is the prototypic member of the serine protease inhibitor (serpin) superfamily of proteins, which has a major role in inactivating neutrophil elastase and other proteases to maintain protease-antiprotease balance. In this study, the serum AAT was measured using enzymatic assay in diabetic patients. The serum trypsin inhibitory capacity (s-TIC) was determined in 144 outpatients with uncontrolled insulin-dependent diabetes mellitus (n=47) and non-insulin dependent diabetes mellitus (n=97). The s-TIC values were 1.960+/-0.399, 2.002+/-0.4304 and 2.867+/-0.395 micromol/min/ml in IDDM, NIDDM and healthy subjects, respectively. The diabetics individual had a significantly lower s-TIC than controls (P<0.0001). It was found that there was a negative correlation between the s-TIC and the duration of diabetes (r=-0.5420; P<0.0001). There was no correlation between s-TIC and age of patients (P=0.865). Thus, diabetes is associated with reduced trypsin inhibitory capacity of plasma.
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PMID:Impaired activity of serum alpha-1-antitrypsin in diabetes mellitus. 1687 54

Glucagon-like peptide-1 (GLP-1) (7-36) is a type of incretin hormone with unique antidiabetic potential. The introduction of orally active GLP-1 offers substantial benefits in the treatment of type 2 diabetes over conventional injection-based therapies. Because the intestinal absorption of GLP-1 is restricted by its natural characteristics, we developed a series of GLP-1 analogues via the site-specific conjugation of biotin-NHS and/or of biotin-poly(ethylene glycol)-NHS at Lys 26 and Lys 34 of GLP-1 (7-36), respectively, in order to improve oral delivery. The resultant GLP-1 analogues, Lys 26,34-DiBiotin-GLP-1 (DB-GLP-1) and Lys 26-Biotin-Lys 34-(Biotin-PEG)-GLP-1 (DBP-GLP-1), were prepared and studied in terms of their chemical, structural, and biological properties. DBP-GLP-1 demonstrated superior proteolytic stability against trypsin, intestinal fluid, and the major GLP-1 inactivation enzyme (dipeptidyl peptidase-IV (DPP-IV)) to native GLP-1 or DB-GLP-1 ( p < 0.001). The in vitro insulinotropic effects of DB-GLP-1 and DBP-GLP-1 showed potent biological activity in a dose-dependent manner, which resembled that of native GLP-1 in terms of stimulating insulin secretion in isolated rat islets of Langerhans. Intraperitoneal glucose tolerance tests (IPGTT) after the oral administration of GLP-1 analogues in diabetic db/db mice demonstrated that DB-GLP-1 and DBP-GLP-1 significantly reduced the AUC 0-180 min of glucose for 3 h by 14.9% and 24.5% compared to that of native GLP-1, respectively ( p < 0.01). In particular, DBP-GLP-1 concentration in plasma rapidly increased 30 min after oral administration in rats, presumably due to improved intestinal absorption. These findings revealed that site-specific biotinylated and biotin-PEGylated GLP-1 is absorbed by intestine and that it has biological activity in vivo. Therefore, we propose that this orally active bioconjugated GLP-1 might be considered as a potential oral antidiabetic agent for type 2 diabetes mellitus.
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PMID:Preparation, characterization, and application of biotinylated and biotin-PEGylated glucagon-like peptide-1 analogues for enhanced oral delivery. 1807 8


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