02264nas 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<p>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.</p>
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-diabetic02638nas a2200277   4500008004100000022001400041245011500055210006900170260000900239300001100248490000900259520174400268653000802012653001302020653001402033653001802047653001202065653000902077100002202086700002302108700002102131700003202152700002202184700002502206856012902231       2021                        eng d  a0925-443900aMolecular investigation of glycated insulin-induced insulin resistance via insulin signaling and AGE-RAGE axis0 aMolecular investigation of glycated insulininduced insulin resis  cFEB   a1660290 v18673 a<p>Hyperglycemic condition in diabetes promotes glycation of various plasma proteins including insulin. Glycation of insulin has been reported to reduce its biological activity. Reduced biological activity of glycated insulin could be either due to reduced affinity for the insulin receptor and impaired insulin signaling, or it can act as a ligand for the receptor for advanced glycation end products (RAGE) and activates oxidative stress and pro-inflammatory pathways leading to insulin resistance. This study investigates the effect of glycated insulin on both insulin and RAGE signaling. Glycated insulin treatment to Chinese hamster ovary (CHO-IR-GLUT4) cells stably expressing insulin receptor (IR) and glucose transporter fused with a green fluorescent protein (GLUT4-GFP) resulted in the impairment of insulin signaling, as the phosphorylation of IR and AKT significantly reduced, which affected GLUT4 translocation and glucose uptake. Moreover, it also activated RAGE signaling as observed by increased expression of NADPH oxidase accompanied by an increase in reactive oxygen species (ROS). Immunofluorescence study indicated the translocation of NF-kappa B to the nucleus upon treatment of glycated insulin. This was associated with increased RAGE expression, Caspase 3, and cell death. Downregulation of RAGE with the losartan treatment restored the impaired insulin signaling and glucose uptake. Additionally, in silico study demonstrated that glycated insulin has reduced binding affinity to insulin receptor and increased binding affinity to RAGE. Overall, this study demonstrates the role of glycated insulin in exacerbating insulin resistance by impairing insulin signaling as well as stimulating AGE-RAGE signaling.</p>
10aAGE10aDiabetes10aGlycation10aHyperglycemia10ainsulin10aRAGE1 aWalke, Prachi, B.1 aBansode, Sneha, B.1 aMore, Nikita, P.1 aChaurasiya, Arvindkumar, H.1 aJoshi, Rakesh, S.1 aKulkarni, Mahesh, J.  uhttps://library.ncl.res.in/content/molecular-investigation-glycated-insulin-induced-insulin-resistance-insulin-signaling-and