Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.2.1.31 (beta-glucuronidase)
 7,680 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report on a 26-yr-old patient with an 11-yr history of insulin-dependent diabetes mellitus who exhibited insulin resistance with a requirement of up to 15,000 U of intravenous (i.v.) insulin/day. Attempts to diminish her insulin requirement by administration of sulfated insulin or Trasylol were unsuccessful, with the patient remaining resistant to subcutaneous (s.c.) and i.v. administration of pure pork insulin. Chloroquine phosphate therapy (500 mg twice a day) resulted in a decreased requirement for i.v. insulin (700 U/day as compared with the pretreatment requirement of 8400 U/day). Accelerated insulin degradation in s.c. fat tissue of the patient before treatment with chloroquine was demonstrated. This activity was decreased by 64% during chloroquine therapy. Inhibition of insulin degrading activity (IDA) during chloroquine therapy was associated with reductions in the leukocyte lysosomal enzymes alpha-galactosidase and hexosaminidase-A but not hexosaminidase-B and beta-glucuronidase. This study constitutes the first reported use of chloroquine for treatment of insulin resistance as a result of accelerated insulin degradation, and it provides evidence of the effectiveness of this agent in this rare condition.
 ...
PMID:In vivo chloroquine-induced inhibition of insulin degradation in a diabetic patient with severe insulin resistance. 609 90

The effect of a 24 hr starvation period on islet lysosomal enzyme activities and the in vivo insulin response to glucose, glibenclamide and L-isopropyl-noradrenaline (L-IPNA) was studied in mice. It was observed that fasting induced a significant decrease of islet acid amyloglucosidase activity, whereas the activities of acid phosphatase, beta-N-acetyl-glucosaminidase, and beta-glucuronidase in islet tissue were unaffected by the fasting period studied. Starvation markedly reduced the acute insulin response to a maximal dose of glucose or glibenclamide. However, the insulin response to a maximal dose of L-IPNA was of similar magnitude in both fed and fasted animals. Pretreatment of fasted mice with purified fungal acid amyloglucosidase could restore the impaired insulin response to glucose to the normal level seen in fed mice. It is suggested that islet acid amyloglucosidase activity is of importance for glucose-stimulated insulin secretion, and that reduced levels of islet amyloglucosidase may contribute to the impairment of glucose-induced insulin release seen after fasting.
 ...
PMID:Effect of fasting on islet lysosomal enzyme activities and the in vivo insulin response to different secretagogues. 640 43

Isolated rats livers were perfused with Krebs-Ringer-Bicarbonate (KRB) and different doses of insulin or glucagon and with insulin plus glucagon. The isolated liver of fasted rats and of rats treated with streptozotocin were perfused with (KRB). The glomerulopressin activity of the ultrafiltrate of the liver perfusates were assayed in the tonic tension contraction (TTC) of isolated stomach fundus from rats. As glomerulopressin is known to be a glucuronide, it was inactivated with beta-glucuronidase to confirm that the effect on the stomach fundus was due to the glomerulopressin and not to an autacoid. It was observed that glucagon increased the glomerulopressin activity of the perfusate and that this activity was independent of the dose of glucagon used. Insulin produced a decrease in the glomerulopressin activity of the perfusate, there being a log-dose relationship between insulin and glomerulopressin. There is a dose of insulin (1,5 X 10(-5) U/min/kg) that potentiates the response to glucagon. Fasting and treatment with streptozotocin induced an increase in the glomerulopressin activity of the perfusate. These results suggest that glomerulopressin production is influenced by glucagon and insulin, and that there is a specific ratio between these hormones that is very effective in the production of glomerulopressin.
 ...
PMID:Influence of insulin and glucagon on the production of glomerulopressin by isolated rat liver. 675 88

The size and polydispersity of insulin granules isolated from rat pancreatic islets by centrifugation on a linear iso-osmotic gradient (300 mosM) have been characterized by quasi-elastic light scattering and photon correlation spectroscopy. The separation of granules by the linear gradient technique was compared directly to isolation on discontinuous gradients of hypertonic sucrose (300-1950 mosM) and the greater efficiency of separation assessed by parallel measurements of protein, insulin, cytochrome oxidase and beta-glucuronidase. Granules isolated from pancreatic beta-cells had a mean particle diameter of 342 nm, buoyant density of 1.104, hydrated mass of 23 femtograms and maximal insulin content of 8-9.6 . 10(5) molecules per granule.
 ...
PMID:Biochemical and biophysical characterization of insulin granules isolated from rat pancreatic islets by an iso-osmotic gradient. 704 89

1 The plasma concentrations of sulphinpyrazone and four of its metabolites are reported together with the amounts excreted in urine. Eight insulin-requiring diabetics were investigated, all treated with sulphinpyrazone 600-800 mg day-1 for 2.5 years or more. 2 Blood samples were drawn before the first morning dose and 2 h later. The mean plasma concentrations were (t=0 h-t=2 h): sulphinpyrazone 7.1-16.0 microgram ml-1; sulphone 1.7-4.8 microgram ml-1; p-OH-sulphide 0.67-0.89 microgram ml-1; p-OH-sulphinpyrazone 0.10-0.16 microgram ml-1. Statistically significant correlations were found between the plasma concentrations at t=0 of the sulphide and the p-OH-sulphide and that of sulphinpyrazone. 3 In urine, a very wide range in excretion of unconjugated compounds was observed. Sulphinpyrazone were excreted in amounts corresponding to 1-30% of the daily dose. The metabolites were generally excreted to amounts corresponding to less than 1% of the daily dose; however, up to 3% was found as the sulphone. 4 Increases of the concentration of all compounds in urine were found after treatment with beta-glucuronidase indicating 0-conjugation with glucuronic acid. 5 Since both the sulphide and the sulphone were found more active as inhibitors of platelet function in vitro than their parent compound, they may together constitute the major part of the platelet inhibitory drug activity in plasma during long-term therapy with sulphinpyrazone.
 ...
PMID:Sulphinpyrazone metabolism during long-term therapy. 727 76

The serum activities of two lysosomal enzymes, beta-N-acetylglucosaminidase (EC 3.2.1.30, NAG) and beta-glucuronidase (EC 3.2.1.31, GLU), were determined in 41 insulin-dependent diabetics, 27 age-matched non-diabetic first-degree relatives of the diabetics and 103 age-matched non-diabetic blood-donors. The diabetics were divided into three groups on the basis of ophthalmoscopy: (1) no retinal abnormalities; (2) non-proliferative retinopathy; and (3) proliferative retinopathy. The activities of both serum enzymes were higher in diabetics (NAG 21.39 +/- 5.99; GLU 2.19 +/- 1.01) than in their relatives (NAG 17.22 +/- 3.99; GLU 1.62 +/-0.61). The diabetics with non-proliferative retinopathy had higher serum enzyme levels (NAG 24.05 +/- 6.26; GLU 2.60 +/- 1.06) than diabetics without retinopathy (NAG 17.88 +/- 3.00; GLU 1.69 +/ 0.64), whereas no statistically significant difference was found in patients with the proliferative form of retinopathy (NAG 18.67 +/- 6.28; GLU 1.99 +/- 1.04). In diabetics a positive correlation was found between serum beta-N-acetylglucosaminidase activity and blood glucose (p < 0.01), but not between beta-glucuronidase and blood glucose. Furthermore, the activities of both enzymes in diabetics correlated with the plasma triglyceride level (p < 0.05 for both correlations). No correlation was found between the enzyme levels and signs of other diabetic late complications.
 ...
PMID:beta-N-acetylglucosaminidase and beta-glucuronidase activities in insulin-dependent diabetic subjects with retinopathy. 741 53

The possible mechanism of diabetic serum factor (DSF)-mediated lysosomal degranulation has been investigated. It was observed that pertussis toxin, sodium fluoride and vanadate could significantly inhibit DSF-mediated beta-glucuronidase release, whereas atropine exhibited only a partial blockage against DSF. Since DSF can generate toxic free radicals, various free radical quenchers were tested in order to evaluate their contributions. Superoxide dismutase was found to be the most effective in inhibiting lysosomal release as compared to catalase and peroxidase. The mixtures of all the enzymes failed to exhibit any additive effect. Interaction of DSF with heparin, insulin and Con A revealed that heparin can completely block DSF-mediated lysosomal release. The implications of the observations are discussed.
 ...
PMID:A mechanistic approach into a diabetic serum factor-mediated release of beta-glucuronidase in normal neutrophils. 785 43

The activities of three lysosomal hydrolases and creatinine levels were measured in the plasma and urine of 11 adults (mean age, 28.1 years) with insulin-dependent diabetes mellitus and 14 non-diabetic controls (mean age, 27.9 years). All of the patients were free of diabetic complications and non exhibited microalbuminuria. Fractional enzyme excretion (FEE) values between the two groups of subjects were calculated and compared for the following enzymes: beta-hexosaminidase (N-acetyl-glucosaminidase), beta-glucuronidase and alpha-galactosidase. The FEE value was calculated as the ratio of enzyme clearance to creatinine clearance. Relative to the non-diabetic control group, the FEE value for beta-hexosaminidase was approximately 2-fold lower (P = 0.02) in the diabetic subjects (means, 0.424 vs. 0.242, respectively). The FEE values for beta-glucuronidase and alpha-galactosidase were not significantly different (P > 0.4) between the diabetic and control groups. These easily measured biochemical parameters in blood and urine and the resultant FEE value for beta-hexosaminidase may provide a means of assessing subtle deteriorative changes in renal function which occur in the early stage of diabetes before the onset of clinically evident complications.
 ...
PMID:Decreased renal excretion of beta-hexosaminidase in adults with insulin-dependent diabetes mellitus and normal renal function. 822 63

The expression of genes encoding conglutin gamma and a leginsulin-like protein has been examined in narrow-leafed lupin, Lupinus angustifolius L. Conglutin gamma is a homologue of basic 7S globulin (Bg), the insulin and leginsulin binding protein from soybean. Accumulation of conglutin gamma mRNA, as assessed by northern assays and reverse-transcription PCR, was tightly regulated both spatially and temporally in lupin plants and was detected almost exclusively in developing seeds. Similar tissue and temporal specificity was demonstrated when 1.8 kb of the promoter region from the conglutin gamma gene was used to drive the expression of a beta-glucuronidase reporter gene in transgenic plants. In stably transformed tobacco the conglutin gamma promoter produced strong, temporally regulated and seed-specific expression of the reporter gene which was localised to the embryo tissues and to a layer of cells adjacent to the seed coat. A truncated 0.29 kb promoter fragment produced much reduced levels of expression and a loss of embryo specificity. Leginsulin-like mRNA was similarly detected in lupins only in developing seeds. The leginsulin-like gene detected in L. angustifolius showed 96% sequence identity to leginsulin from soybean within the 280 bp region amplified from lupin by PCR. The results demonstrate that both components of a Bg-leginsulin putative signal transduction pathway are present in the seeds of lupin.
 ...
PMID:Transcription of genes for conglutin gamma and a leginsulin-like protein in narrow-leafed lupin. 924 43

Accumulated evidence links an important signal involved in glucose-stimulated insulin release to the activation of the islet lysosomal glycogenolytic enzyme acid glucan-1,4-alpha-glucosidase. We have analyzed the function of the lysosomal system/lysosomal enzyme activities in pancreatic islets of young (6-8 weeks), spontaneously diabetic, GK (Goto-Kakizaki) rats and Wistar control rats in relation to glucose-induced insulin release. The insulin secretory response to glucose was markedly impaired in the GK rat, but was restored by the adenylate cyclase activator forskolin. Islet activities of classical lysosomal enzymes, e.g.. acid phosphatase, N-acetyl-beta-D-glucosaminidase, beta-glucuronidase, and cathepsin D, were reduced by 20-35% in the GK rat compared with those in Wistar controls. In contrast, the activities of the lysosomal alpha-glucosidehydrolases, i.e.. acid glucan-1,4-alpha-glucosidase and acid alpha-glucosidase, were increased by 40-50%. Neutral alpha-glucosidase (endoplasmic reticulum) was unaffected. Comparative analysis of liver tissue showed that lysosomal enzyme activities were of the same magnitude in GK and Wistar rats. Notably, in Wistar rats, the activities of acid glucan-1,4-alpha-glucosidase and acid alpha-glucosidase were approximately 15-fold higher in islets than in liver. Other lysosomal enzymes did not display such a difference. Normalization of glycemia in GK rats by phlorizin administered for 9 days did not influence either the lysosomal alpha-glucosidehydrolase activities or other lysosomal enzyme activities in GK islets. Finally, the pseudotetrasaccharide acarbose, which accumulates in the lysosomal system, inhibited acid glucan-1,4-alpha-glucosidase activity in parallel with its inhibitory action on glucose-induced insulin release in intact Wistar islets, whereas no effect was recorded for either parameter in intact GK islets. In contrast, acarbose inhibited the enzyme activity equally in islet homogenates from both GK and Wistar rats, showing that the catalytic activity of the enzyme itself in disrupted cells was unaffected. We propose that dysfunction of the islet lysosomal/vacuolar system is an important defect impairing the transduction mechanisms for glucose-induced insulin release in the GK rat.
 ...
PMID:Dysfunction of the islet lysosomal system conveys impairment of glucose-induced insulin release in the diabetic GK rat. 1038 96


<< Previous 1 2 3 Next >>