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 accumulation of glycation derived cross-links has been widely implicated in extracellular matrix damage in aging and diabetes, yet little information is available on the cross-linking sites in proteins and the intra- versus intermolecular character of cross-linking. Recently, glucosepane, a 7-membered heterocycle formed between lysine and arginine residues, has been found to be the single major cross-link known so far to accumulate during aging. As an approach toward identification of glucose derived cross-linking sites, we have preglycated ribonuclease A first for for 14 days with 500 mM glucose, followed by a 4-week incubation in absence of glucose. MALDI-TOF analysis of tryptic digests revealed the presence of Amadori products (Delta m/ z = 162) at K1, K7, K37 and K41, in accordance with previous studies. In addition, K66, K98 and K104 were also modified by Amadori products. Intramolecular glucosepane cross-links were observed at K41-R39 and K98-R85. Surprisingly, the only intermolecular cross-link observed was the 3-deoxyglucosone-derived DODIC at K1-R39. The identity of cross-linked peptides was confirmed by sequencing with tandem mass spectrometry. Recombinant ribonuclease A mutants R39A, R85A, and K91A were produced, purified, and glycated to further confirm the importance of these sites on protein cross-linking. These data provide the first documentation that both intramolecular and intermolecular cross-links form in glucose-incubated proteins.
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PMID:Identification of glucose-derived cross-linking sites in ribonuclease A. 1850 Aug 35

A rapid and specific analytical method for simultaneous determination and quantification of seven major phospholipid classes in human blood was developed by normal-phase high-performance liquid chromatography tandem mass spectrometry. The optimal separation was achieved by using mobile phase hexane (A) and 2-propanol with water, formic acid and ammonia as modifiers (B) using an HPLC diol column. Isocratic elution method was used for better repeatability and no balance time. The seven major phospholipid classes in human blood that were detected including phosphatidylserine (PS), phosphatidylethanolamine (PE), phosphatidylglycerol (PG), phosphatidylinositol (PI) phosphatidylcholine (PC), lysophosphatidylcholine (Lyso-PC), and sphingomyelin (SM). That can be separated in this condition. Every phospholipid class contains many molecular species which have similar structure. The structure of phospholipids molecular species was identified by ion-trap MS(n) which produced ion fragments. And the qualification was completed by TOF-MS which shows good accuracy. Through the accurate quantification of one representative phospholipids molecule in each class, a method for simultaneous estimation hundreds of molecular species in seven major classes was established. The intra-day and inter-day precision and recovery had been investigated in detail. The RSD of precision for most compound is below 8% and RE is below 10%. Recovery is almost over 80%. This method was applied to phospholipids disorder related with diabetes nephropathy successfully. The concentrations of most phospholipids for normal people are higher than that for diabetic nephropathy (DN) patients in three phases. For most of phospholipids, with the development of DN the concentration was decreasing.
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PMID:Simultaneous determination and quantification of seven major phospholipid classes in human blood using normal-phase liquid chromatography coupled with electrospray mass spectrometry and the application in diabetes nephropathy. 1852 99

A histidine-tagged recombinant N-terminal fragment of type-1 mouse liver diacylglycerol acyltransferase (DGAT; EC 2.3.1.20), MmDGAT1(1-95)His6, was expressed in Escherichia coli, and used to investigate possible acyl-CoA-binding properties. Analysis of the purified fragment by MALDI-TOF mass spectrometry revealed a polypeptide with molecular mass of about 11 kDa which was consistent with the calculated molecular mass based on the deduced amino acid sequence. Lipidex-1000 binding assays indicated that MmDGAT1(1-95)His(6) interacted with long chain fatty acyl-CoAs similar to observations on DGAT1 from oilseed rape (Brassica napus). Binding, as a function of acyl-CoA concentration, differed for palmitoyl (16:0), stearoyl (18:0), and erucoyl (cisDelta(13)22:1)-CoA. Binding of stearoyl- or erucoyl-CoA to MmDGAT1(1-95)His(6) as a function of acyl-CoA concentration, however, was sigmoid and displayed positive cooperativity suggesting that MmDGAT1 may be subject to allosteric modulation by acyl-CoAs. An intra-polypeptide segment within the N-terminal region of MmDGAT1 contained remnants of an acyl-CoA-binding signature initially identified in plant DGAT1. The acyl-CoA-binding site in mammalian DGAT1 could represent a potential target for therapeutic interventions for disorders such as type-2 diabetes and obesity.
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PMID:An N-terminal fragment of mouse DGAT1 binds different acyl-CoAs with varying affinity. 1857

Type 2 diabetes (T2D) is a very heterogeneous and multifactorial disease. The pathophysiology of T2D is presumed to occur with an alteration in the levels of plasma proteins. To identify these differentially expressed proteins, plasma samples from normal and T2D humans were subjected to two-dimensional gel electrophoresis, quantitative densitometry, and mass spectrometry. Up to 200 protein spots were visible on each gel, of which 57 appeared modulated in diabetic individuals. Subsequently, 31 spots with > or =2-fold change in their expression were analyzed by MALDI-TOF mass spectrometry leading to the identification of 11 proteins with average sequence coverage of approximately 38%. The expression of apolipoprotein A-I was reduced by 4.2-fold, and galectin-1 was increased 4.8 times in diabetic samples. Induction of galectin-1 in T2D samples was confirmed by ELISA. In addition, the dose-dependent treatment of rat L6 skeletal muscle cells with glucose resulted in an upregulation of galectin-1. These data implicate the association of galectin-1 with the pathophysiology of diabetes and identify galectin-1 as a novel diagnostic marker protein in T2D patients.
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PMID:Proteomics-based identification of differentially-expressed proteins including galectin-1 in the blood plasma of type 2 diabetic patients. 1912 85

A series of dinuclear copper(II) complexes involving 6-(benzylamino)purine derivatives, (HL(n)), as bridging ligands were synthesized, characterized and tested for both their in vitro and in vivo antioxidant activities. Based on results of elemental analyses, temperature dependence of magnetic susceptibility measurements, UV-vis, FTIR, EPR, NMR and MALDI-TOF mass spectroscopy, conductivity measurements and thermal analyses, the complexes with general compositions of [Cu(2)(mu-HL(n))(4)Cl(2)]Cl(2).2H(2)O (1-4) and [Cu(2)(mu-HL(n))(2)(mu-Cl)(2)Cl(2)] (5-7) were prepared {where n=1-4; HL(1)=6-[(2-methoxybenzyl)amino]purine, HL(2)=6-[(4-methoxybenzyl)amino]purine, HL(3)=6-[(2,3-dimethoxybenzyl)amino]purine and HL(4)=6-[(3,4-dimethoxybenzyl)amino]purine}. In the case of complexes 2, 3, 5 and 7, the antioxidant activities were studied by both in vitro {superoxide dismutase-mimic (SOD-mimic) activity} and in vivo {cytoprotective effect against the alloxan-induced diabetes (antidiabetic activity)} methods. The obtained IC(50) value of the SOD-mimic activity for the complex 5 (IC(50)=0.253 microM) was shown to be even better than that of the native bovine Cu,Zn-SOD enzyme (IC(50)=0.480 microM), used as a standard. As for the antidiabetic activity, the pretreatment of mice with complexes 3 and 7 led to the complete elimination of cytotoxic attack of alloxan and its free radical metabolites, used as a diabetogenic agent. The cytoprotective effect of these compounds was proved by the preservation of the initial blood glucose levels of the pretreated animals, as against the untreated control group.
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PMID:Dinuclear copper(II) complexes containing 6-(benzylamino)purines as bridging ligands: synthesis, characterization, and in vitro and in vivo antioxidant activities. 1917 83

Insulinoma NIT-1, an insulin-secreting mouse cell line, secretes vesicles in response to glucose or calcium. These vesicles, like exosomes, are relatively homogeneous (30-100 nm). We analyzed their protein profiles employing one-dimensional SDS gel electrophoresis combined with nanoLC-ESI-q-TOF tandem mass spectrometry, and searched for post-translational modifications (PTMs) using MOD(i) algorithm. We identified 270 proteins which matched at least two peptides reproducibly in duplicate runs. These proteins included metabolic proteins, endocytosis/exocytosis related proteins, chaperones, cytoskeletal proteins, membrane transporters/ion channels, signaling molecules, and nucleic acid binding proteins. Over 200 of these are newly identified proteins for the first time in secreted vesicles, and included RNA- and translation-related proteins, ubiquitin- and protein-degradation related proteins and post-translationally modified proteins. The rest of the proteins identified in this study were similar to those reported by others to be present in exosomes of various origins. The present study demonstrates that vesicles secreted from insulinoma NIT-1 cells have some properties, common to exosomes from lymphocytes and cancer cells, and some differing from those of other types of exosomes. We believe that the modified and newly identified proteins we identified in secreted vesicles from insulinoma NIT-1 cells have the potential to provide insights into mechanisms of biogenesis and function of secreted vesicles and may help explain the impairment of insulin secretion in islets from type-2 diabetes.
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PMID:Characterization of vesicles secreted from insulinoma NIT-1 cells. 1935 Nov 51

Islet Neogenesis Associated Protein (INGAP) is implicated in pancreatic islet neogenesis. INGAP peptide, a pentadecapeptide comprising amino acids 104-118, reverses diabetes in rodents and improves glucose homeostasis in patients with diabetes. The mechanism of INGAP action is unknown, but such studies would benefit from the availability of the full-length recombinant protein (rINGAP). Here we report the production of rINGAP from 293-SF cells following lentiviral transduction, and its characterization by MALDI-TOF and Q-TOF Mass Spectrometry, and HPLC. Importantly, we show that rINGAP exhibits 100x the bioactivity of INGAP peptide on a molar basis in an in vitro assay of human islet regeneration.
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PMID:Production and characterization of the recombinant Islet Neogenesis Associated Protein (rINGAP). 1963 67

Diabetic nephropathy is one of the most common complications of diabetes mellitus and the leading cause of end-stage renal disease. A reduction in podocyte number has been documented in the kidneys of these patients. To identify the molecular changes in podocytes that are primarily caused by high glucose (HG) concentrations and not by secondary alterations (e.g. glomerular hypertension), we investigated the protein expression profiles in a podocyte cell line under long-term HG exposure (30 versus 10 mM for 2 wk). Proteins were separated by 2-DE, and we identified 39 different proteins in 48 spots that were differentially regulated by more than twofold in response to HG concentrations using MALDI-TOF MS and MASCOT software. These proteins belong to several protein classes, including cytoskeletal proteins and specific annexins (annexins III and VI). Downregulation of annexins III and VI by HG concentrations was confirmed by qRT-PCR, Western blot, and immunostaining, and was also observed in glomeruli of kidney biopsies from patients with diabetic nephropathy. Our data demonstrate that HG concentrations per se are sufficient to strongly modify the protein expression profile of podocytes, the analysis of which contributes to the identification of novel targets involved in diabetic nephropathy.
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PMID:Alterations of the podocyte proteome in response to high glucose concentrations. 1968 24

Green (reagents and organic solvents saving) analytical chemistry is a new strategy for pharmaceutical analysis. The principles of this idea include primary elimination or at least reduction of the amounts of organic reagents and solvents. In this study, we have provided two simple methods for the analysis of clinical drugs in human plasma. One is the capillary LC (Cap LC) connected to MS-MS, the other is the matrix-assisted laser desorption ionization (MALDI) connected to TOF MS. Sulfonylurea drugs are usually used in diabetes mellitus patients. Diabetes is a syndrome of disordered metabolism resulting in abnormally high blood sugar levels (hyperglycemia). These microscale methods were successfully applied for the monitoring of drug levels in human plasma using gliclazide (a second-generation sulfonylurea) as the test platform. The sensitivity of these methods is sufficient for detecting the gliclazide within a therapeutic range. All the analytical procedures (including human plasma, sample preparation, and flow rate of the analytical system) were at microscale level. These two methods would lower the consumption of organic solvents further safeguarding our environment.
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PMID:Trace analysis of glyclazide in human plasma at microscale level by mass spectrometry. 1976 53

Discovery of protein biomarkers in different diseases is an important area of research in the field of proteomics. We have described the levels of protein biomarkers specific to diabetes mellitus type 2 in the local population of Pakistan using proteomic technology. Type 2 diabetic patients, age and sex-matched normal healthy controls were recruited from Sheikh Zayed Hospital, Lahore, Pakistan. Plasma proteins were analysed by 2D liquid chromatographic system in which samples were initially fractionated by chromatofocusing and the selected fractions were further analysed by reverse-phase high performance liquid chromatography. The proteins which showed variation between test and control samples were identified by MALDI-TOF analysis. All the samples belonging to the control and diabetic groups were then analyzed by ELISA and estimated four proteins which were found to vary. Levels of apolipoprotein A-I was found to decrease by -6.4% while apolipoprotein E, leptin and C reactive protein (CRP) were increased by +802, +842 and +872%, respectively, in the diabetic patients as compared to the controls. The discovery of these marker proteins might thus provide an adjunctive method for early detection of risk for this disease.
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PMID:Proteomic identification of human serum biomarkers in diabetes mellitus type 2. 2001 4


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