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)

Interleukin-6 (IL-6) is a pleiotropic cytokine which has been proposed as "cytokine for gerontologists" and linked to age-related metabolic disturbances such as the metabolic syndrome or type 2 diabetes. Polymorphisms located in the promoter region of IL-6 have been reported to be involved in the regulation of IL-6 transcription. This study investigates whether IL-6 promoter variants -174 G/C and -573 G/C are associated with quantitative traits related to the metabolic syndrome (International Diabetes Federation criteria) in a population of normoglycemic subjects (n=878) from the latest KORA survey (KORA S4). Genotyping was performed using MALDI-TOF MS. Besides lower height (p=0.01) the -174 CC genotype was independently associated with lower waist (p=0.002) and hip (p=0.01) circumferences in men. Furthermore, the -174 CC genotype was associated with BMI (p=0.004) when adjusted for waist and hip circumference. The present study does not suggest associations with further components of the metabolic syndrome. The association with height seems to be the central factor indicating an influence of IL-6 on growth through impaired bone metabolism. However, the complex relationships need further investigation.
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PMID:IL-6 promoter polymorphisms and quantitative traits related to the metabolic syndrome in KORA S4. 1679 5

Protein glycation by methylglyoxal is a nonenzymatic post-translational modification whereby arginine and lysine side chains form a chemically heterogeneous group of advanced glycation end-products. Methylglyoxal-derived advanced glycation end-products are involved in pathologies such as diabetes and neurodegenerative diseases of the amyloid type. As methylglyoxal is produced nonenzymatically from dihydroxyacetone phosphate and d-glyceraldehyde 3-phosphate during glycolysis, its formation occurs in all living cells. Understanding methylglyoxal glycation in model systems will provide important clues regarding glycation prevention in higher organisms in the context of widespread human diseases. Using Saccharomyces cerevisiae cells with different glycation phenotypes and MALDI-TOF peptide mass fingerprints, we identified enolase 2 as the primary methylglyoxal glycation target in yeast. Two other glycolytic enzymes are also glycated, aldolase and phosphoglycerate mutase. Despite enolase's activity loss, in a glycation-dependent way, glycolytic flux and glycerol production remained unchanged. None of these enzymes has any effect on glycolytic flux, as evaluated by sensitivity analysis, showing that yeast glycolysis is a very robust metabolic pathway. Three heat shock proteins are also glycated, Hsp71/72 and Hsp26. For all glycated proteins, the nature and molecular location of some advanced glycation end-products were determined by MALDI-TOF. Yeast cells experienced selective pressure towards efficient use of d-glucose, with high methylglyoxal formation as a side effect. Glycation is a fact of life for these cells, and some glycolytic enzymes could be deployed to contain methylglyoxal that evades its enzymatic catabolism. Heat shock proteins may be involved in proteolytic processing (Hsp71/72) or protein salvaging (Hsp26).
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PMID:Yeast protein glycation in vivo by methylglyoxal. Molecular modification of glycolytic enzymes and heat shock proteins. 1706 14

The SELDI-TOF technique was used to profile serum proteins from Type 1 diabetes (T1D) patients and healthy autoantibody-negative (AbN) controls. Univariate and multivariate analyses were performed to identify putative biomarkers for T1D and to assess the reproducibility of the SELDI technique. We found 146 protein/peptide peaks (581 total peaks discovered) in human serum showing statistical differences in expression levels between T1D patients and controls, with 84% of these peaks showing technical replication. Because individual proteins did not offer great power for disease prediction, we used our model averaging approach that combines the information from multiple multivariate models to accurately classify T1D and control subjects (88.9% specificity and 90.0% sensitivity). Analyses of a test subset of the data showed less accuracy (82.8% specificity and 76.2% sensitivity), although the results are still positive. Unfortunately, no multivariate model could be replicated using the same samples. This first attempt of high throughput analyses of the human serum proteome in T1D patients suggests that model averaging is a viable method for developing biomarkers; however, the reproducibility of SELDI-TOF is currently not sufficient to be used for classification of complex diseases like T1D.
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PMID:Assessing the utility of SELDI-TOF and model averaging for serum proteomic biomarker discovery. 1709 16

Protein profiling would aid in better understanding the pathophysiology of metabolic disease. Here, we report on differential proteomic analysis using an animal model of diabetes mellitus and associated metabolic disorders (Otsuka Long-Evans Tokushima Fatty rat). Serum was analyzed by a new two-dimensional liquid chromatography system which separated proteins by chromatofocusing and subsequent reversed-phase chromatography. This is the first application of this approach to differential serum proteomics. Differentially expressed proteins, identified with MALDI-TOF mass spectrometry, included apolipoproteins and alpha2-HS-glycoprotein. These findings add to our understanding of the underlying pathophysiology. This new proteomic analysis is a promising tool to elucidate disease mechanisms.
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PMID:Differential serum proteomic analysis in a model of metabolic disease. 1709 53

Proteinchip profiling is a powerful and innovative proteomic technology for biomarker discovery and diagnostic/prognostic assay development. Based on surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS), Ciphergen's proteinchip system offers a single, unified, high-throughput platform for a multitude of proteomic research applications. Proteins are the major functional components of the cell, the study of proteomics provides mankind with a better understanding of disease and life. The remarkable findings in disease biomarkers have shed light to the early diagnosis, monitoring and predicting prognosis of various diseases, especially for cancer. In this article, the development and technology of SELDI-TOF MS are introduced. Some research progress and encouraging research results in oncoproteomics, infectious diseases, neurological diseases and diabetes mellitus using SELDI-TOF MS are also reviewed. The paper is closed by the appraisals on its pros and cons, as well as the future prospective is also expounded.
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PMID:[Research progress in SELDI-TOF MS and its clinical applications]. 1716 5

Diabetic nephropathy (DN) is a renal disease which develops as a consequence of diabetes mellitus. Microalbuminuria is the earliest clinical sign of DN. There are no specific diagnostic biomarkers for type 2 diabetics with nephropathy other than microalbuminuria and macroalbuminuria. However, microalbuminuria does not constitute a sole independent indicator for type 2 diabetics with nephropathy, and thus, another screening method, such as a biomarker assay, is required in order to diagnose it more correctly. Therefore, we have utilized two-dimensional electrophoresis (2-DE) to identify human serum protein markers for the more specific and accurate prediction of progressive nephropathy in type 2 diabetes patients, via comparisons of the serum proteome in three experimental groups: type 2 diabetes patients without microalbuminuria (DM, n = 30), with microalbuminuria (MA, n = 29), and with chronic renal failure (CRF, n = 31). As a result, proteins which were differentially expressed with statistical significance (p < 0.05) in MA and CRF groups as compared to those in DM group were selected and identified by ESI-Q-TOF MS/MS. Among these identified proteins, two proteins which might be useful as diagnostic biomarkers of type 2 diabetics with nephropathy were verified by Western blotting: extracellular glutathione peroxidase (eGPx) and apolipoprotein (ApoE) were found to exhibit a progressive reduction in MA and CRF groups. Notably, eGPx was further verified by ELISA using DM (n = 100) and MA (n = 96) patient samples. Collectively, our results show that the two proteins identified in this study may constitute potential biomarkers for the diagnosis of type 2 diabetics with nephropathy.
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PMID:Proteome analysis of serum from type 2 diabetics with nephropathy. 1726 29

In this study, proteomic analysis was performed on the skin of C57BL/6J mice with type 2 diabetes and compared to nondiabetic controls. To induce obesity and subsequent diabetes, mice were placed on a high-fat diet for 16 wk. After 16 wk, both diabetic and nondiabetic control mice were sacrificed and their skin removed for analysis. Following 2-DE, proteomic profiles from the skin samples were quantified using PDQuest software. Out of more than 1000 distinct protein spots, 28 were shown to be significantly altered with 6 being decreased and 22 increased in the diabetic state compared to controls. The 28 protein spots were removed from the gels and analyzed by MALDI-TOF and MS/MS analyses. Protein identifications revealed that 17 of the 28 proteins were involved in energy metabolism (60.7% of changes observed). Collectively, none of the significantly altered proteins had been shown previously to be altered in diabetic skin. This study not only helps to identify proteins found in skin samples of obese mice with type 2 diabetes, but also shows that skin biopsies coupled with proteomic analysis may be useful as a noninvasive method for the diagnosis of hyperinsulinemia and diabetes.
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PMID:Analysis of mouse skin reveals proteins that are altered in a diet-induced diabetic state: a new method for detection of type 2 diabetes. 1739 Feb 96

To understand the spectrum of proteins affected by diabetes and to characterize molecular functions and biological processes they control, we analyzed the renal cortical proteome of db/db mice using 2-DE combined with MALDI-TOF, MALDI-TOF/TOF, and LC-MS/MS. This approach yielded 278 high confidence identifications whose expression levels were significantly increased or decreased >two-fold by diabetes, of which 170 mapped to gene identifiers representing 147 nonredundant proteins. Gene Ontology classification demonstrated that 80% of these proteins modulated physiological functions, 55% involved metabolism, approximately 25% involved carboxylic and organic acid metabolism, 14% involved biosynthesis or catabolism, and 12% involved fatty acid metabolism. Predominant molecular functions were catalytic (61%), oxidoreductase (20%), and transferase (17%) activities, and nucleotide and ATP binding (11-15%). Twenty eight percent of the proteins identified as significantly altered by diabetes were mitochondrial proteins. The top-ranked network described by Ingenuity Pathway Analysis indicated PPARalpha was the most common node of interaction for the numerous enzymes whose expression levels were influenced by diabetes. These differentially regulated proteins create a foundation for a systems biology exploration of molecular mechanisms underlying the pathophysiology of diabetic nephropathy.
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PMID:Diabetes-induced changes in the renal cortical proteome assessed with two-dimensional gel electrophoresis and mass spectrometry. 1743 68

Diabetic nephropathy is a common diabetic complication that is associated with alterations in the expression of several renal proteins and abnormal calcium homeostasis. We performed proteomic analysis to screen for global changes of renal protein expression in diabetic kidney. Proteins extracted from the whole kidney of 120-day-old OVE26 (a transgenic model of Type 1 diabetes) and FVB (non-diabetic background strain) mice were separated by two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) and visualized by SYPRO Ruby staining (n = 5 in each group). Quantitative intensity analysis revealed 41 differentially expressed proteins, of which 30 were identified by matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF MS) followed by peptide mass fingerprinting. One of the altered proteins with the greatest magnitude of change was the calcium-binding protein, calbindin-D28k, whose expression was increased 6.7-fold in diabetic kidney. We confirmed the increase in calbindin-D28k expression in diabetic kidney by Western blot analysis. Immunohistochemical study demonstrated that calbindin-D28k expression was markedly increased in tubular epithelial cells of distal convoluted tubules (DCT), collecting ducts (CD), and proximal convoluted tubules (PCT) in diabetic kidney. Calbindin-D28k plays a critical role in maintaining calcium homeostasis. The elevation in renal calbindin-D28k expression in our model may indicate a compensatory mechanism to overcome hypercalciuria in diabetes.
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PMID:Proteomic identification and immunolocalization of increased renal calbindin-D28k expression in OVE26 diabetic mice. 1749 55

To study the change in hepatic stellate cell (HSC) function under diabetic conditions, we cultured rat HSC in the presence of 5 and 30 mM glucose, which correspond to blood glucose concentrations during the early and late stages of diabetes, respectively. The differentially expressed HSC proteins were analyzed using 2-DE and ESI-Q-TOF MS/MS and confirmed with Western blotting. The changed protein expression will provide greater understanding of glycolysis in HSC at the high concentration of glucose.
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PMID:Proteome analysis of the rat hepatic stellate cells under high concentrations of glucose. 1754 97


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