UMLS:C0011849 - FACTA Search

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

Query: UMLS:C0011849 (diabetes)
277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We studied the effect of supplementation with vitamins C, E and beta-carotene (PARABION, produced by Syndipharma) on antioxidative status in kidneys of male Wistar rats with diabetes induced by intravenous application of streptozotocin (45 mg.kg-1 of body weight). The animals received subtherapeutic doses of Insulin Interdep (6 U.kg-1 of body weight). A significant decrease of malondialdehyde (MDA), reduced (GSH) and oxidized (GSSG) glutathione and reduction of the activities of Se-glutathione peroxidase (Se-GSH-PX, EC. 1.11.1.9.) and glutathione S-transferase (GST, EC. 2.5.1.18.) were observed in kidneys of diabetic rats treated with these vitamins. On the contrary, the activity of CuZn-superoxide dismutase (CuZn-SOD, EC. 1.15.1.1) and the level of vitamin C (vit. C) increased significantly. No changes were observed for vitamin E (vit. E), beta-carotene and catalase (CAT, EC. 1.11.1.6). Supplementation with vitamins C, E and beta-carotene resulted in an improvement of antioxidative status of kidneys of rats with streptozotocin-induced diabetes.
...
PMID:Effect of intake of exogenous vitamins C, E and beta-carotene on the antioxidative status in kidneys of rats with streptozotocin-induced diabetes. 747 41

The erythrocytes from control (C), diabetic (D) and insulin-treated diabetic (D+I) rats were separated into three ageing groups (TAG) i.e., light dense (young cells), intermediate-dense (middle-aged cells) and heavy-dense (old aged cells) samples. The activities of enzymes and metabolites changed from young to old cells in the following manner: (1) Increase of CAT in TAG and a lower level in D and D+I (2) Decrease of GPx in TAG but a low level in D (3) Increase of GR in TAG but a higher level in D, (4) Increase of GST in C and a decrease in D with a higher level in young cells and a lower level in middle-aged and old cells. The reversal of enzyme was more in young cells of D+I (5) Increase of GSH in TAG, a low level in D and a high level in D+I (6) Increase of GSSG in TAG, a high level found only in young cells of D. The results show that young red cells are affected more significantly in diabetes than other age cell types.
...
PMID:Ageing erythrocytes and alloxan diabetes: I. A possible role of catalase, GSH, GSSG, and GSH-enzymes in decreasing defence system. 829 96

Recently, a new subfamily of Ras-related GTP-binding proteins consisting of Rad (Ras associated with diabetes), Gem (immediate early gene expressed in mitogen-stimulated T-cells), and Kir (tyrosine kinase-inducible Ras-like) was discovered. The C terminus of these proteins contains an extension of approximately 30 amino acids not present in other members of the Ras family and which exhibits all the hallmarks typical for calmodulin (CaM)-binding domains. A peptide corresponding to the putative CaM-binding domain of the Kir/Gem protein was synthesized, and its affinity for CaM was determined by fluorescence spectrometry. Titration of dansyl-CaM with the Kir/Gem peptide gave an affinity constant of 1 nM. Furthermore, a single point mutation of the peptide, W269G, abolished this high affinity interaction. Gel-shift analysis showed that the complex formation between CaM and the Kir/Gem peptide is strictly calcium-dependent. We also demonstrate with a newly developed [32P]CaM overlay technique that full-length Kir/Gem and Rad proteins bind CaM in a Ca2+-dependent fashion. The binding of CaM to glutathione S-transferase-Kir and GST-Gem inhibited the binding of GTP to Kir/Gem significantly. These results suggest the existence of a direct link between Ca2+/CaM and growth factor signal transduction pathways at the level of small Ras-like GTPases.
...
PMID:Calmodulin binds to and inhibits GTP binding of the ras-like GTPase Kir/Gem. 881 Feb 59

The placenta possesses the ability to metabolize a number of xenobiotics and endogenous compounds by processes similar to those seen in the liver. Animal and in vivo studies have observed that the presence of diabetes alters the expression of hepatic metabolizing enzymes (cytochrome P450 and glutathione S-transferase); however, it is unknown whether similar alterations occur in the human placenta. To evaluate whether diabetes has any effect of placental xenobiotic metabolizing activity, the catalytic activities of 7-ethoxyresorufin O-deethylation (EROD, CYP1A1), chlorzoxazone 6-hydroxylation (CYP2E1), dextromethorphan N-demethylation (CYP3A4), dextromethorphan O-demethylation (CYP2D6), and 1-chloro-2, 4-dinitrobenzene (CDNB) conjugation with glutathione (glutathione S-transferase, GST) from placentas of diet (class A1) and insulin-dependent (class A2) gestational diabetics and overt diabetics were compared with matched controls. EROD activity (CYP1A1) ranged from 0.29 to 2.67 pmol/min/mg protein. However, no differences were observed among overt or gestational diabetics and their respective matched controls. CDNB conjugation (GST) ranged from 0.275 to 1.65 units/min/mg protein. In contrast to that observed with CYP1A1, a small but statistically significant reduction in GST activity was noted in overt diabetics as compared with their matched controls and gestational diabetics. CYP2E1, 2D6, and 3A4 enzymatic activities were not detected in human placental tissue. GST protein was detectable in all tissues studied, but no CYP protein could be detected in any of the tissues. Thus, it seems that pregnant women with overt diabetes have reduced GST activity in the placenta, which could potentially result in the exposure of the fetus to harmful electrophiles. However, the full clinical significance of this finding remains to be elucidated.
...
PMID:Effects of gestational and overt diabetes on human placental cytochromes P450 and glutathione S-transferase. 953 26

In 32 published reports in surgical patients, the preponderance of evidence from standard clinical measures of renal function (BUN and Cr) indicates the absence of renal toxicity following sevoflurane anesthesia. Studies of surgical patients receiving intermediate-duration sevoflurane with high or low fresh gas flow and long-duration sevoflurane with high fresh gas flow included sensitive measures of renal function and/or injury, which also indicate the absence of renal toxicity following sevoflurane anesthesia. Studies of surgical patients receiving long-duration sevoflurane with low fresh gas flow did not include sensitive measures. Seven studies in volunteers are not directly relevant to clinical practice but do raise the issue of whether it is important to apply sensitive measures of renal function and/or injury such as urine concentrations and/or excretion of NAG, beta 2M, alpha 1M, AAP, alpha GST, pi GST, gamma GTP, albumin, protein, and glucose and Cr clearance. Two studies of volunteers receiving prolonged sevoflurane anesthesia with fresh gas flow no greater than 2 L/min concluded that the potential for adverse renal effects of sevoflurane may exist. The other studies of volunteers did not. In 14 published reports of surgical patients in special conditions, the preponderance of evidence from standard clinical measures of renal function indicates the absence of renal toxicity. Studies with sensitive measures have been reported for some conditions where the kidney may be at increased risk (e.g., sevoflurane-induced hypotension, advanced age, and renal insufficiency and failure), are incomplete in others (e.g., hypertension and ischemic heart disease), and are missing in others (e.g., morbid obesity). Studies with sensitive measures of renal function and/or injury are also missing in an important group where the kidney may not be at increased risk--pediatric patients. Studies of other risk conditions, such as temporary ischemia, hemorrhagic hypotension, nephrotoxic antibiotics, kidney transplantation, and diabetes may provide additional information about the renal effects of sevoflurane.
...
PMID:Renal effects of sevoflurane during conditions of possible increased risk. 980 93

Hyperglycemia is observed in some patients with autoimmune bullous diseases complicated by diabetes mellitus or treated with systemic corticosteroids. High concentrations of glucose can react with various proteins and change their structural and functional properties. We previously reported that nonenzymatic glycosylation of antibody can impair antigen-antibody binding. We ascertained whether glycosylation of autoantibody decreases the autoantibody titer by examining 30 sera from patients with pemphigus and pemphigoid. Nonenzymatic glycosylation in the physiological range was induced by incubation of sera with 1650 mM D-glucose at 4 degrees C for 7 days. The titers of sera were determined by indirect immunofluorescence (IIF). In all cases, the immunofluorescence intensity of glycosylated sera was weaker than that of nonglycosylated sera. Glycosylated sera showed a lower antibody titer by 1 doubling dilution in 18 out of 30 cases, compared with nonglycosylated sera. The ten BP patients' sera were also analyzed by immunoblotting for reactivity with the BP180-GST fusion proteins, S delta 1 and 4575. All BP sera reacted with S delta 1, and 5 out of 10 BP sera reacted with both S delta 1 and 4575. In all the sera that reacted only with S delta 1, the glycosylated sera showed a 1 doubling dilution decrease in autoantibody titer. Interestingly, in 4 out of 5 sera that reacted with both S delta 1 and 4575, there were no differences in the antibody titer between glycosylated and nonglycosylated sera. These results indicate the possibility of a false decrease in autoantibody titers of sera from patients with autoimmune bullous diseases complicated with hyperglycemia. Although the false decrease in titers of autoantibodies induced by nonenzymatic glycosylation is not dramatic, it must be considered in order not to underestimate the disease activity of pemphigus in such cases.
...
PMID:Effect of nonenzymatic glycosylation on the titers of circulating autoantibodies in pemphigus and pemphigoid. 986 83

The receptors for activated C-kinase (RACK) family of proteins function as anchors for activated protein kinase C (PKC) isoenzymes. Using a monoclonal antibody to RACK1 in the screening of a human hippocampus cDNA library, we identified a novel member of the RACK family, designated PRKCBP1. Immunoprecipitation assays performed with a GST-fused PRKCBP1 protein suggest the carboxy terminus of PRKCBP1 interacts specifically with PKCbetaI. Northern analysis detected a 3.1-kb PRKCBP1 transcript in all tissues examined including brain, heart, liver, lung, pancreas, skeletal muscle, kidney, and spleen. The PRKCBP1 gene has been localized to human Chromosome (Chr) 20q12-13.1. Several groups have reported evidence for genetic linkage of Type II diabetes to this region in Caucasian families. This localization, combined with the observation that abnormalities in the activation, translocation, and inhibition of PKC occur in the development of Type II diabetes, suggested that PRKCBP1 was a candidate for contributing to Type II diabetes. We determined the PRKCBP1 coding sequence is 1845 bp in length, dispersed over 9 exons, spanning approximately 34 kb of genomic DNA. SSCP analysis was used to screen PRKCBP1 coding regions for mutations or polymorphisms in 100 Caucasian Type II diabetics and 100 Caucasian unaffected individuals. A silent C/T transition (bp1413, Thr137) was present in 23% of both diabetic and control individuals. A C/T transition (bp198) was also identified in a single diabetic individual, which resulted in no coding change (Ser66). The results of this analysis suggest that PRKCBP1 coding variations are uncommon and do not contribute to Type II diabetes in the general population.
...
PMID:Identification and characterization of PRKCBP1, a candidate RACK-like protein. 1100 9

Nonobese diabetic (NOD) mice develop insulitis and diabetes through a process involving autoimmunity to the 60-kDa heat shock protein (HSP60). Treatment of NOD mice with HSP60 or with peptides derived from HSP60 inhibits this diabetogenic process. We now report that NOD diabetes can be inhibited by vaccination with a DNA construct encoding human HSP60, with the pcDNA3 empty vector, or with an oligonucleotide containing the CpG motif. Prevention of diabetes was associated with a decrease in the degree of insulitis and with down-regulation of spontaneous proliferative T cell responses to HSP60 and its peptide p277. Moreover, both the pcDNA3 vector and the CpG oligonucleotide induced specific Abs, primarily of the IgG2b isotype, to HSP60 and p277, and not to other islet Ags (glutamic acid decarboxylase or insulin) or to an unrelated recombinant Ag expressed in bacteria (GST). The IgG2b isotype of the specific Abs together with the decrease in T cell proliferative responses indicate a shift of the autoimmune process to a Th2 type in treated mice. These results suggest that immunostimulation by bacterial DNA motifs can modulate spontaneous HSP60 autoimmunity and inhibit NOD diabetes.
...
PMID:Vaccination with empty plasmid DNA or CpG oligonucleotide inhibits diabetes in nonobese diabetic mice: modulation of spontaneous 60-kDa heat shock protein autoimmunity. 1108 48

Protein tyrosine phosphatases are a class of enzymes that function to modulate tyrosine phosphorylation of cellular proteins and play an essential role in regulating cell function. PTP1B has been implicated in the negative regulation of the insulin signaling pathway by dephosphorylating the activated insulin receptor. Inhibiting this phosphatase and preventing the insulin-receptor downregulation has been suggested as a target for the treatment of Type II diabetes. A high-throughput screen for inhibitors of PTP1B was developed using a scintillation proximity assay (SPA) with GST-- or FLAG--PTP1B((1-320)) and a potent [(3)H]-tripeptide inhibitor. The problem of interference from extraneous oxidizing and alkylating agents which react with the cysteine active-site nucleophile was overcome by the use of the catalytically inactive C215S form of the native enzyme (GST--PTP1B(C215S)). The GST--PTP1B was linked to the protein A scintillation bead via GST antibody. The radiolabeled inhibitor when bound to the enzyme gave a radioactive signal that was competed away by the unknown competitive compounds. Further utility of PTP1B(C215S) was demonstrated by mixing in the same well both the catalytically inactive GST--PTP1B(C215S) and the catalytically active FLAG--CD45 with an inhibitor. Both a binding and kinetic assay was then performed in the same 96-well plate with the inhibition results determined for the PTP1B(C215S) (binding assay) and CD45 (activity assay). In this way inhibitors could be differentiated between the two phosphatases under identical assay conditions in one 96-well assay plate. The use of a mutant to reduce interference in a binding assay and compare with activity assays is also amenable for most cysteine active-site proteases.
...
PMID:Development of a robust scintillation proximity assay for protein tyrosine phosphatase 1B using the catalytically inactive (C215S) mutant. 1140 1

Even small increases in the frequency of thrombotic disease in users of OCs have general health impact because of their widespread use, which is currently expanding to potential risk groups. The present investigations were launched to study the effects of OCs containing 20-40 micrograms of EE combined with the latest developed gonane progestogens on biochemical risk markers within metabolic systems involved in the development of arterial thrombotic disease. The studies included evaluation of carbohydrate and lipid metabolism as well as the haemostatic system and were performed in non-diabetic women and in women with IDDM, who are prone to the development of arterial thrombosis. In the evaluation of the carbohydrate metabolism in non-diabetic women, we found no effect on fasting glucose or insulin and no effect on the insulin response to oral glucose in women using monophasic OCs containing EE combined with DSG or GST. This contrasts the evaluation of triphasic OCs containing EE combined with GST or NGT, which increased fasting insulin and reduced insulin sensitivity without affecting the glucose-effectiveness or the beta-cell function. Impaired glucose tolerance developed in 10% of the women after 6 months. These finding suggest that OCs are able to induce a state of insulin resistance, which should be considered in the prescription for women with potential disturbed insulin sensitivity or reduced beta-cell secretory capacity e.g. women with ovarian hyperandrogenism, obesity, previous GDM or perimenopausal women. We found no change in glycaemic control in 22 women with well-regulated IDDM treated with a monophasic combination of EE and GST for one year and none of the women developed microalbuminuria during treatment. In the women with diabetes we observed an increase in fasting levels of triglycerides, a decrease in LDL-cholesterol, and unchanged concentrations of total cholesterol and HDL-cholesterol during treatment. In non-diabetic women treated with the same compound or an OC containing EE and DSG we found similar changes in triglycerides and total cholesterol, but increased levels of HDL-cholesterol and unchanged LDL-cholesterol concentrations. In the women with IDDM there was a negative correlation between daily insulin requirement and HDL-cholesterol before and during treatment, but no other statistically significant correlation between estimates of glycaemic control and lipids and lipoproteins were observed. In the non-diabetic women, changes in the haemostatic system included an increase in the procoagulant factors fibrinogen and Factor VIIc; the concentration of active t-PA increased, mainly because of decreased inhibition by PAI-1. The ratio between molecular markers of the activity of the coagulation system and the efficacy of fibrinolysis was unchanged. This was also found in the women with IDDM, who showed evidence of increased fibrin formation and an attenuated fibrinolytic response during treatment. The regulation of the t-PA/PAI system was studied in non-diabetic women in order to elucidate if the effects of OCs are caused by a direct effect on synthesis or clearance of these variables or if they are secondary to changed insulin sensitivity, as described in individuals with atherosclerosis. We found no indications that insulin resistance is involved in the regulation of t-PA and PAI-1 antigen levels, neither before nor during intake of OCs. We showed, however, that the decreased t-PA antigen concentration observed in OC users is caused by reduced synthesis outside the splanchnic circulation. The studies indicate that low-dose OCs containing newer gonane progestogens are able to induce insulin resistance and to impair glucose tolerance. Lipoproteins were not adversely influenced by the OCs neither in the diabetic nor the non-diabetic women; on the contrary, there was a tendency towards increased plasma levels of HDL-cholesterol and decreased LDL-cholesterol which are associated with a decreased risk of atherosclerosis. The changes observed within the haemostatic system were in accordance with a maintained balance between coagulation and fibrinolysis although the rate of fibrin formation may be increased in the women with IDDM. Irrespective of OC use, the interrelationships between metabolic systems in young non-diabetic women are different from those reported in individuals with atherosclerosis or insulin resistance. The effects of OCs on the t-PA/PAI system seem to be mediated by a direct effect on the vessel wall and not by changes in the hepatic clearance. The present findings were obtained in diabetic women without vascular complications, so the conclusion that women with IDDM can use OCs without metabolic alterations of known clinical significance is therefore restricted to those without evidence of diseased vessels. When evaluating the results obtained in the non-diabetic women, it should be remembered that women with recognised risk factors were excluded. The results may therefore be of limited value when evaluating the risk of arterial thrombosis in predisposed populations. In healthy individuals, the present integrated evaluation of biochemical markers does not indicate an increased risk of arterial thrombosis during use of low-dose OCs containing newer gonane progestogens; thus, the findings are in accordance with the recent epidemiological studies on these compounds. The application of relevant biochemical markers facilitate the understanding of the non-reproductive effects of sex steroids which have increasing importance because of their expanding use, not only as contraceptives, but also in the treatment of benign gynaecological disorders, as hormone replacement therapy and as prophylactic agents against specific degenerative conditions. Moreover, they may prove to be helpful in the future identification of women, who have increased susceptibility to the metabolic effects of sex steroids due to genetic predisposition.
...
PMID:Pharmacodynamic effects of oral contraceptive steroids on biochemical markers for arterial thrombosis. Studies in non-diabetic women and in women with insulin-dependent diabetes mellitus. 1189 23

1 2 3 4 5 6 Next >>