Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aim of the study was to validate clinically a new technique of myocardial protection developed for intra- and extra-cardiac surgery on the beating heart. The concept combines the principle of continuous pressure- and volume-controlled coronary artery perfusion (PVC-CONTHY-CAP) with the specific myocardioprotective effects of hypothermia and nitrates and, on the other hand, with the beta-blocker-mediated reduction of chronotropy and inotropy necessary for convenient surgery. Under standard ECC conditions after cross-clamping the aorta coronary perfusion with oxygenated blood enriched with nitroglycerine (10 micrograms/kg/h) and esmolol (0.05 mg/ml flow/min) is started via an additional perfusion cannula placed in the aortic root. The temperature of the perfusate is maintained at 32 degrees C, the intraaortic pressure at 40-70 mmHg and the perfusion flow in the range 0.8-1.0 ml/g heart muscle/min. In CABG procedures an additional perfusion catheter is used for perfusion of distal coronary artery segments. Using this technique 100 consecutive patients, adults and children, were operated on between 2/96 and 8/96. In 84 adult patients (age: 45-82 yrs), 78 CABG procedures (54 elective, 13 urgent, 11 acute) with a mean bypass count of 3.7 (range 1-7), 69 ITA grafts, 72 grafts to CX, and 3 MVRec/MVRpl, and 6 pure MVRec/MVRpl procedures (1 urgent, 1 emergency) were performed. The mean coronary perfusion time was 48 min (range 21-88 min). In 5 patients perioperative infarction (CABG; 1 emergency after PTCA, 4 elective) with significant increase of CK-MB values (57-98 U/L) occurred. In the 4 elective patients (3 with diabetes mellitus) re-intervention was not possible due to small-vessel disease. In one patient with preoperative infarction IABP was necessary. No patient died. There were 16 children (age: 4weeks-16 yrs): VSD, n = 6, AV-C, n = 2, TOF, n = 1, MVRec, n = 1, DORV (Rastelli), n = 2, SV (TCPC), n = 3, and PV obstruction, n = 1. The mean coronary perfusion time was 97 min (range: 27-260 min). The mean ICU stay 3.9 d (range: 1-10 d). One child died (TCPC) on the 10th postoperative day due to multi-organ failure. In conclusion, PVC-CONTHY-CAP is designed especially for emergency and urgent procedures, i.e. patients with PTCA-related complications, patients with severely depressed LV function, and patients with complex congenital cyanotic heart defects. Using PVC-CONTHY-CAP, coronary artery bypass grafting as well as intracardiac procedures for congenital and acquired heart defects can be performed safely and conveniently, the system is easy to handle for both the cardiac surgeon and perfusionist. Due to its pharmacological properties continuous intracoronary application of nitrates in combination with hypothermia seems to be essential as a preventive treatment modality for the ischemic state.
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PMID:Myocardial protection by pressure- and volume-controlled continuous hypothermic coronary perfusion (PVC-CONTHY-CAP) in combination with ultra-short beta-blockade and nitroglycerine. 917 18

Methylglyoxal (MG), a physiological alpha-dicarbonyl compound is derived from glycolytic intermediates and produced during the Maillard reaction. The Maillard reaction, a non-enzymatic reaction of ketones and aldehydes with amino group of proteins, contributes to the aging of proteins and to complications associated with diabetes. In our previous studies (Che, et al. (1997) "Selective induction of heparin-binding epidermal growth factor-like growth factor by MG and 3-deoxyglucosone in rat aortic smooth muscle cells. The involvement of reactive oxygen species formation and a possible implication for atherogenesis in diabetes". J. Biol. Chem., 272, 18453-18459), we reported that MG elevates intracellular peroxide levels, but the mechanisms for this remain unclear. Here, we report that MG inactivates bovine glutathione peroxidase (GPx), a major antioxidant enzyme, in a dose- and time-dependent manner. The use of BIAM labeling, it was showed that the selenocysteine residue in the active site was intact when GPx was incubated with MG. MALDI-TOF-MS (matrix-assisted laser desorption/ionization time-of-flight mass spectrometry) and protein sequencing examined the possibility that MG modifies arginine residues in GPx. The results show that Arg 184 and Arg 185, located in the glutathione binding site of GPx was irreversively modified by treatment with MG. Reactive dicarbonyl compounds such as 3-deoxyglucosone, glyoxal and phenylglyoxal also inactivated GPx, although the rates for this inactivation varied widely. These data suggest that dicarbonyl compounds are able to directly inactivate GPx, resulting in an increase in intracellular peroxides which are responsible for oxidative cellular damage.
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PMID:Identification of the binding site of methylglyoxal on glutathione peroxidase: methylglyoxal inhibits glutathione peroxidase activity via binding to glutathione binding sites Arg 184 and 185. 1265 9

Resistin, a small cysteine rich protein secreted by adipocytes, has been proposed to be a link between obesity and type II diabetes by modulating the insulin signaling pathway and thus inducing insulin resistance. Resistin protein, with 11 cysteine residues, was not significantly homologous at the amino acid level to any other known cysteine rich proteins. Resistin cDNA derived from human subcutaneous adipose tissue was expressed in Escherichia coli as an N-terminal six-His-tag fusion protein. The overexpressed recombinant resistin was purified to homogeneity from inclusion bodies, after solubilization in 8 M urea, using a metal affinity column. While MALDI-TOF mass spectrometric analysis of the purified protein generated a single peak corresponding to the estimated size of 11.3 kDa, the protein exhibited a concentration-dependent oligomerization which is evident from size exclusion chromatography. The oligomeric structure was SDS-insensitive but beta-mercaptoethanol-sensitive, pointing to the importance of disulfide linkages in resistin oligomerization. Estimation of free cysteine residues using the NBD-Cl assay revealed a concentration- and time-dependent increase in the extent of formation of disulfide linkages. The presence of intermolecular disulfide bond(s), crucial in maintaining the global conformation of resistin, was further evident from fluorescence emission spectra. Circular dichroism spectra revealed that recombinant resistin has a tendency to reversibly convert from alpha-helical to beta-sheet structure as a direct function of protein concentration. Our novel observations on the biophysical and biochemical features of human resistin, particularly those shared with prion proteins, may have a bearing on its likely physiological function.
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PMID:Human recombinant resistin protein displays a tendency to aggregate by forming intermolecular disulfide linkages. 1296 78

The term protein glycation summarizes non-enzymatic reactions between amino groups of proteins and sugars or sugar degradation products, leading to early glycation products (intact sugar attached) and advanced glycation end-products (AGEs). Protein glycation is involved in the progression of several diseases, such as diabetes, uremia, and atherosclerosis. However, qualitative and quantitative analysis of in vitro or in vivo glycated proteins is still a challenging task. The introduction of matrix-assisted laser desorption ionization time-of-flight technique (MALDI-TOF) changed mass spectrometry (MS) into a valuable tool for biomedical analysis, because the soft ionization procedure allows the measurement of proteins up to 100 kDa. In the last few years, MALDI-TOF-MS was applied to the investigation of glycation processes: the analyses of plasma proteins from diabetic or uremic patients allowed a precise determination of the average number of sugar residues attached to serum albumin or immunoglobulins of each patient. Thus, a more individualized diagnosis of each patient was achieved by MALDI-TOF-MS than by other diagnostic tools. In a similar way, the glycation rate of hemoglobin, isolated from diabetic blood and of beta-2-microglobulin isolated from amyloid plaques from uremic patients was determined. The application of MALDI-TOF-MS for in vitro studies revealed important new insights into glycation mechanisms. Whereas the measurement of the intact proteins allows the determination of the average glycation rate, peptide mapping prior to MALDI-TOF-MS can reveal the exact structures of the glycation products and the glycation site. Furthermore, when the unmodified peptide is used as internal standard, MALDI-TOF-MS can also be used for reliable, site specific relative quantification of defined glycation products.
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PMID:Analysis of protein glycation products by matrix-assisted laser desorption ionization time-of-flight mass spectrometry. 1527 57

Erythritol is a noncariogenic, low calorie sweetener. It is safe for people with diabetes and obese people. Candida magnoliae is an industrially important organism because of its ability to produce erythritol as a major product. The genome of C. magnoliae has not been sequenced yet, limiting the available proteome database. Therefore, systematic approaches were employed to construct the proteome map of C. magnoliae. Proteomic analysis with systematic approaches is based on two-dimensional electrophoresis, matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF MS), tandem mass spectrometry (MS/MS) and database interrogation. First, 24 spots were analyzed using peptide mass fingerprinting along with MALDI-TOF MS with high mass accuracy. Only four spots were reliably identified as carbonyl reductase and its isoforms. The reason for low sequence coverage seemed to be that these identification strategies were based on the presence of the protein database obtained from the publicly accessible genome database and the availability of cross-species protein identification. MS/MS (MS/MS ion search and de novo sequencing) in combination with similarity searches allowed successful identification of 39 spots. Several proteins including transaldolase identified by MS/MS ion searches were further confirmed by partial sequences from the expressed sequence tag database. In this study, 51 protein spots were analyzed and then potentially identified. The identified proteins were involved in glycolysis, stress response, other essential metabolisms and cell structures.
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PMID:Strategic proteome analysis of Candida magnoliae with an unsequenced genome. 1537 35

The quantization of glycated isoforms of hemoglobin has been increasingly used in clinical practice in recent years. Glycated hemoglobin is currently considered the most important measurement for long-term control of the glycemic state and it has become a reference tool for the management of diabetes. Glutathionylated hemoglobin is an increasingly clinically relevant covalent adduct of glutathione with beta chain of the globin and its concentration has been correlated with oxidative stress. We have developed an innovative technique based on linear mode matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry for quantitative analysis of hemoglobin species. This method was applied to the quantification of glycated and glutathionylated hemoglobin. A rigorous comparison was pursued to evaluate the analytical performances in quantifying glycated hemoglobin in comparison to an established high-performance liquid chromatography method. Our results indicated a complete equivalence between the two methods. The same analysis enabled the quantitative determination of the glutathionylated hemoglobin fraction. This isoform was investigated in an adult Italian population (184 individuals, 101 males and 83 females), indicating a bimodal distribution of this species. In fact 65.22% of screened individuals had glutathionylated hemoglobin levels lower than 0.50% while 34.78% had glutathionylated hemoglobin levels higher than 0.50%. A semiautomatic robotic procedure was developed for fast analysis of a large number of samples. This is the first report of a quantitative application of linear MALDI-TOF mass spectrometry for the determination of glutathionylated hemoglobin in blood samples. This method allows fast screening of this hemoglobin isoform, therefore opening the route to explore its specificity and sensitivity as a molecular biomarker.
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PMID:A quantitative method for the analysis of glycated and glutathionylated hemoglobin by matrix-assisted laser desorption ionization-time of flight mass spectrometry. 1562 Aug 93

Glucagon-like peptide-1-(7-36) (GLP-1) is a hormone derived from the proglucagon molecule, which is considered a highly desirable antidiabetic agent mainly due to its unique glucose-dependent stimulation of insulin secretion profiles. However, the development of a GLP-1-based pharmaceutical agent has a severe limitation due to its very short half-life in plasma, being primarily degraded by dipeptidyl peptidase IV (DPP-IV) enzyme. To overcome this limitation, in this article we propose a novel and potent DPP-IV-resistant form of a poly(ethylene glycol)-conjugated GLP-1 preparation and its pharmacokinetic evaluation in rats. Two series of mono-PEGylated GLP-1, (i) N-terminally modified PEG(2k)-N(ter)-GLP-1 and (ii) isomers of Lys(26), Lys(34) modified PEG(2k)-Lys-GLP-1, were prepared by using mPEG-aldehyde and mPEG-succinimidyl propionate, respectively. To determine the optimized condition for PEGylation, the reactions were monitored at different pH buffer and time intervals by RP-HPLC and MALDI-TOF-MS. The in vitro insulinotropic effect of PEG(2k)-Lys-GLP-1 showed comparable biological activity with native GLP-1 (P = 0.11) in stimulating insulin secretion in isolated rat pancreatic islet and was significantly more potent than the PEG(2k)-N(ter)-GLP-1 (P < 0.05) that showed a marked reduced potency. Furthermore, PEG(2k)-Lys-GLP-1 was clearly resistant to purified DPP-IV in buffer with 50-fold increased half-life compared to unmodified GLP-1. When PEG(2k)-Lys-GLP-1 was administered intravenously and subcutaneously into rats, PEGylation improved the half-life, which resulted in substantial improvement of the mean plasma residence time as a 16-fold increase for iv and a 3.2-fold increase for sc. These preliminary results suggest a site specifically mono-PEGylated GLP-1 greatly improved the pharmacological profiles; thus, we anticipated that it could serve as potential candidate as an antidiabetic agent for the treatment of non-insulin-dependent diabetes patients.
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PMID:Synthesis, characterization, and pharmacokinetic studies of PEGylated glucagon-like peptide-1. 1576 92

Adipose tissues play a crucial endocrine role in the control of whole body glucose homeostasis and insulin sensitivity. Considering the current substantial rise in obesity and obesity-related diseases, including diabetes, it is important to understand the molecular basis of adipocyte differentiation and its control. In this study, we have analyzed the protein expression inherent to adipogenic differentiation, by 2-DE, MALDI-TOF, and RT-PCR. This study focused on proteins that were differentially expressed by the differentiation of human mesenchymal stem cells (hMSCs) to adipocytes. We conducted 2-DE for each set of proteins in the cytosol of adipocytes that had differentiated from hMSC, in a pH range from 3-10. Thirty-two protein spots were shown to have different expression levels. Among these, eight up-regulated proteins were identified by MALDI-TOF/MS, as the following: syntaxin binding protein 3, OSBP-related protein 3, phosphodiesterase, glycophorin, immunoglobulin kappa chain variable region, peroxisome proliferative activated receptor gamma (PPAR-gamma), bA528A10.3.1 (novel protein similar to KIAA01616, isoform 1), and T cell receptor V-beta 4. Four proteins: syntaxin-3, OSBP-related protein 3, PPAR-gamma and glycophorin were associated with adipogenesis.
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PMID:The proteomic analysis of an adipocyte differentiated from human mesenchymal stem cells using two-dimensional gel electrophoresis. 1642 33

Diabetes mellitus (DM) is a chronic progressive disease that often results in microvascular and macrovascular complications, yet its pathogenesis is not clear. Automated proteomic technology, coupled with powerful bioinformatics and statistical tools, can provide new insights into the molecular alterations implicated in DM. Following our previous findings of redox changes in the eye and aorta of diabetic rats, as well as the activities of different antioxidant enzymes during the development of DM, this study is further launched to find potential biomarkers by comparing the serum and tissue samples of 26 diabetic rats (8 weeks after streptozotocin [STZ] administration) with 29 normal controls using surface enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) technology. Eight potential biomarkers were found in the serum, one potential biomarker was found in the kidney and eye, respectively, whereas three potential biomarkers were discovered in the aorta. One of the serum biomarker candidates was found to match the C-reactive protein (CRP) in the Swiss-Prot knowledgebase. Further validation has been conducted by ELISA kit to confirm the role of CRP during the development of DM. To conclude, the increased level of CRP in diabetic serum demonstrated in this study indicates that the development of DM is associated with inflammation. This is also the first report demonstrating that some potential lysate biomarkers in the kidney, eye, and aorta may be involved in the development of diabetes and its complications. Further identification and evaluation of these potential biomarkers will help unravel the underlying mechanisms of the disease.
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PMID:Differential expression of proteins in kidney, eye, aorta, and serum of diabetic and non-diabetic rats. 1659 75

Diabetes mellitus (DM) is now a global health problem, however, its pathogenesis has not yet been fully deciphered. Even though modern medicine has great contribution to the control and treatment of DM, it is still far from success to completely cure the disease. Panax ginseng C.A. Meyer (ginseng) is a well-recognized traditional Chinese medicine for treating DM in Asia. In this study, high throughput proteomic approach has been adopted to investigate the antidiabetic action of 2 weeks' ginsenoside Re (Re, a major component of ginseng) administration to streptozotocin-induced diabetic rats. Employing surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) and bioinformatics, 432 cluster peaks were detected in the samples, among them 293 potential biomarkers were found to have significant differentiations between the DM and control normal rats. When the Re-treated diabetic rats were compared to the untreated ones, a protein peak was detected to have significant alteration corresponding to Re treatment. This specific protein was found to match with C-reactive protein (CRP) in the protein database, and was subsequently validated by ELISA. This is the first study demonstrated that CRP could be altered by Re treatment, indicating that Re may improve diabetes and its complications by alleviation of inflammation.
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PMID:Altered expression of serum protein in ginsenoside Re-treated diabetic rats detected by SELDI-TOF MS. 1679 97


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