02720nas a2200289 4500008004100000022001400041245015100055210006900206260008100275300002200356490000700378520163500385653001302020653001402033653001402047653002102061653001002082653002202092100003902114700002502153700002502178700002002203700002302223700002902246700002502275856013002300 2016 eng d a1542-641600aTargeted quantification of N-1-(carboxymethyl) valine and N-1-(carboxyethyl) valine peptides of beta-hemoglobin for better diagnostics in diabetes0 aTargeted quantification of N1carboxymethyl valine and N1carboxye a236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLANDbBIOMED CENTRAL LTDcMAR aArticle Number: 70 v133 a

Background: N-1-(Deoxyfructosyl) valine (DFV) beta-hemoglobin (beta-Hb), commonly referred as HbA1c, is widely used diagnostic marker in diabetes, believed to provide glycemic status of preceding 90-120 days. However, the turnover of hemoglobin is about 120 days, the DFV-beta-Hb, an early and reversible glycation product eventually may undergo irreversible advanced glycation modifications such as carboxymethylation or carboxyethylation. Hence quantification of N-1-(carboxymethyl) valine (CMV) and N-1-(carboxyethyl) valine (CEV) peptides of beta-Hb would be useful in assessing actual glycemic status. Results: Fragment ion library for synthetically glycated peptides of hemoglobin was generated by using high resolution-accurate mass spectrometry (HR/AM). Using parallel reaction monitoring, deoxyfructosylated, carboxymethylated and carboxyethylated peptides of hemoglobin were quantified in clinical samples from healthy control, pre-diabetes, diabetes and poorly controlled diabetes. For the first time, we report N-1-beta-valine undergoes carboxyethylation and mass spectrometric quantification of CMV and CEV peptides of beta-hemoglobin. Carboxymethylation was found to be the most abundant modification of N-1-beta-valine. Both CMV-beta-Hb and CEV-beta-Hb peptides showed better correlation with severity of diabetes in terms of fasting glucose, postprandial glucose and microalbuminuria. Conclusions: This study reports carboxymethylation as a predominant modification of N-1-beta-valine of Hb, and quantification of CMV-beta-Hb and CEV-beta-Hb could be useful parameter for assessing the severity of diabetes.

10aDiabetes10aDiagnosis10aGlycation10aGlycemic control10aHbA1c10aMass spectrometry1 aJagadeeshaprasad, Mashanipalya, G.1 aBatkulwar, Kedar, B.1 aMeshram, Nishita, N.1 aTiwari, Shalbha1 aKorwar, Arvind, M.1 aUnnikrishnan, Ambika, G.1 aKulkarni, Mahesh, J. uhttps://library.ncl.res.in/content/targeted-quantification-n-1-carboxymethyl-valine-and-n-1-carboxyethyl-valine-peptides-beta02404nas a2200169 4500008004100000245007900041210006900120260000800189300001600197490000600213520177800219100003901997700003102036700002902067700002502096856011302121 2018 eng d00a Albumin abundance and its glycation Status determine hemoglobin glycation0 aAlbumin abundance and its glycation Status determine hemoglobin  cOCT a12999-130080 v33 aDiabetes diagnosis and management majorly depend upon the measurement of glycated hemoglobin (HbAlc) levels. Various factors influence HbAlc levels such as the use of various analytical methods and the presence of various clinical conditions. Plasma albumin levels were known to be negatively associated with HbAlc. However, the precise mechanism by which they affect HbAlc is not well' understood. Therefore, we have studied the influence of albumin levels and its glycation status on hemoglobin glycation using erythrocyte culture experiments. Erythrocytes maintained at low albumin concentration exhibited relatively increased albumin and hemoglobin glycation as compared to that in those maintained at higher albumin concentration. Increase in albumin glycation may decrease its ability to protect hemoglobin glycation. This was demonstrated by treatment of erythrocytes with N(epsilon-(carboxymethyl)lysine-modified serum albumin (CMSA), which failed to protect hemoglobin glycation; instead, it increased hemoglobin glycation. The inability of CMSA to reduce hemoglobin glycation was due to the lack of free lysine residues of albumin, which was corroborated by using N(epsilon-(acetyI)lysine serum albumin (AcSA) and clinical diabetic plasma. This is the first study which demonstrates that the modification of lysine residues of albumin impairs its ability to inhibit hemoglobin glycation. Furthermore, correlation studies between HbAlc and albumin levels or relative albumin fructosamine from clinical subjects supported our experimental finding that albumin abundance and its glycation status influence hemoglobin glycation. Therefore, we propose albumin level and its glycation status to be quantified in conjunction with HbAlc for better management of diabetes.1 aJagadeeshaprasad, Mashanipalya, G.1 aVenkatasubramani, Vinashya1 aUnnikrishnan, Ambika, G.1 aKulkarni, Mahesh, J. uhttps://library.ncl.res.in/content/albumin-abundance-and-its-glycation-status-determine-hemoglobin-glycation02264nas a2200217 4500008004100000022001400041245011500055210006900170260000900239300001600248490000600264520148300270100002001753700003201773700002001805700002201825700001801847700002901865700002501894856012701919 2020 eng d a2470-134300aCD44, a predominant protein in methylglyoxal-induced secretome of muscle cells, is elevated in diabetic plasma0 aCD44 a predominant protein in methylglyoxalinduced secretome of  cOCT  a25016-250280 v53 a

Methylglyoxal (MG), a glycolytic intermediate and reactive dicarbonyl, is responsible for exacerbation of insulin resistance and diabetic complication. In this study, NIG-induced secretome of rat muscle cells was identified and relatively quantified by SWATH-MS. A total of 643 proteins were identified in MG induced' secretome, of which 82 proteins were upregulated and 99 proteins were downregulated by more than 1.3-fold in SWATH analysis. Further, secretory proteins from the dassical secretory pathway and nonclassical secretory pathway were identified using SignalP and SecretomeP, respectively. A total of 180 proteins were identified with SignalP, and 113 proteins were identified with SecretomeP. The differentially expressed proteins were functionallyannotated by KEGG pathway analysis using Cytoscape soft ware with plugin clusterMaker. The differentially expressed proteins were'sfound to he involved m various pathways like extracellular matrix (ECM) receptor interaction, leukocyte transendothelial migration, fluid shear tress and atherosclerosis, complement and coagulation cascades, and lysosomal pathway. Since the MG levels are high in diabetic conditions, the presence of MG-induced isecreted proteins was inspected `by profiling human plasma of healthy and diabetic subjects (n = 10 each). CD44, a predominant MG -induced secreted protein, was found to be elevated in the diabetic plasma and to have a role in the development of insulin resistance.

1 aBai, Shakuntala1 aChaurasiya, Arvindkumar, H.1 aBanarjee, Reema1 aWalke, Prachi, B.1 aRashid, Faraz1 aUnnikrishnan, Ambika, G.1 aKulkarni, Mahesh, J. uhttps://library.ncl.res.in/content/cd44-predominant-protein-methylglyoxal-induced-secretome-muscle-cells-elevated-diabetic01832nas a2200217 4500008004100000022001400041245011300055210006900168260000900237300001600246490000600262520104300268100003201311700002301343700002901366700001801395700002001413700002901433700002501462856012701487 2023 eng d a2470-134300aElevated level of glycated KQTALVELVK peptide of albumin is associated with the risk of diabetic nephropathy0 aElevated level of glycated KQTALVELVK peptide of albumin is asso cJUN  a20654-206600 v83 a

Diabetic nephropathyis a leading cause of end-stagerenal disease.Hence, early detection of diabetic nephropathy is essential to mitigatethe disease burden. Microalbuminuria, the currently used diagnosticmarker of diabetic nephropathy, is not efficient in detecting it atan early stage. Therefore, we explored the utility of glycated humanserum albumin (HSA) peptides for risk prediction of diabetic nephropathy.Three glycation-sensitive HSA peptides, namely, FKDLG-EENFK,KQTAL-VELVK, and KVPQVST-PTLVEVSR, with deoxyfructosyllysine(DFL) modification were quantified by targeted mass spectrometry (MS)in a study population comprising healthy and type II diabetes subjectswith and without nephropathy. Mass spectrometry, receiver operatingcharacteristic (ROC) curve, and correlation analysis revealed thatthe DFL-modified KQTALVELVK peptide was better than other glycatedHSA peptides and HbA(1c) for identifying diabetic nephropathy.DFL-modified KQTALVELVK could be a potential marker for risk predictionof diabetic nephropathy.

1 aChaurasiya, Arvindkumar, H.1 aJaiswal, Meera, R.1 aBayatigeri, Santhakumari1 aKahar, Shweta1 aTiwari, Shalbha1 aUnnikrishnan, Ambika, G.1 aKulkarni, Mahesh, J. uhttps://library.ncl.res.in/content/elevated-level-glycated-kqtalvelvk-peptide-albumin-associated-risk-diabetic-nephropathy02952nas a2200241 4500008004100000022001400041245011100055210006900166260000900235300001600244490000600260520209500266100002902361700002002390700002802410700002402438700002302462700002402485700002002509700002902529700002502558856012702583 2024 eng d a2470-134300aDiscovery of free glycated amines and glycated urea in diabetic plasma: potential implications in diabetes0 aDiscovery of free glycated amines and glycated urea in diabetic  cMAY  a24907-249150 v93 a

The role of protein glycation in the pathogenesis of diabetes has been well established. Akin to proteins, free amino acids and other small-molecule amines are also susceptible to glycation in hyperglycemic conditions and may have a role in the pathogenesis of the disease. However, information about glycation of free amino acids and other small-molecule amines is relatively obscure. In the quest to discover small-molecule glycated amines in the plasma, we have synthesized glycated amino acids, glycated creatine, and glycated urea, and by using a high-resolution accurate mass spectrometer, a mass spectral library was developed comprising the precursor and predominant fragment masses of glycated amines. Using this information, we report the discovery of the glycation of free lysine, arginine, and leucine/isoleucine from the plasma of diabetic patients. This has great physiological significance as glycation of these amino acids may create their deficiency and affect vital physiological processes such as protein synthesis, cell signaling, and insulin secretion. Also, these glycated amino acids could serve as potential markers of diabetes and its complications. While other amines, such as creatinine and urea, accumulate in the plasma and act as biomarkers of diabetic nephropathy. For the first time, we report the detection of glycated urea in diabetic plasma, which is confirmed by matching the precursor and fragment masses with the in vitro synthesized glycated urea by using C-12(6) and C-13(6)-glucose. Further, we quantified glycated urea detected in two forms, monoglycated urea (MGU) and diglycated urea (DGU), by a targeted mass spectrometric approach in the plasma of healthy, diabetic, and diabetic nephropathy subjects. Both MGU and DGU showed a positive correlation with clinical parameters, such as blood glucose and HbA1c. Given that urea gets converted to glycated urea in hyperglycemic conditions, it is crucial to quantify MGU and DGU along with the urea for the diagnosis of diabetic nephropathy and study their physiological role in diabetes.

1 aShaikh, Rashdajabeen, Q.1 aDas, Sancharini1 aChaurasiya, Arvindkumar1 aAshtamy, Murali, G.1 aSheikh, Amreen, B.1 aFernandes, Moneesha1 aTiwari, Shalbha1 aUnnikrishnan, Ambika, G.1 aKulkarni, Mahesh, J. uhttps://library.ncl.res.in/content/discovery-free-glycated-amines-and-glycated-urea-diabetic-plasma-potential-implications