Non-Enzymatic Glycation of Transferrin and Diabetes Mellitus

Abstract

Diabetes is a metabolic disease characterized by high blood sugar. Its complications may damage multiple organs, such as eyes, kidneys, heart, blood vessels, and nerves, severely threatening human health. Transferrin (Tf) is a major iron transport protein in the body. Recent studies have shown that the degree of non-enzymatic glycated modification of Tf is increased in diabetic patients, and glycated Tf is closely related to the occurrence and development of diabetes and diabetic complications. However, the molecular mechanisms underlying this glycated modification in diabetes and diabetic complications are still unclear. It is speculated that the mechanism may be that glycated modification reduces the binding ability of Tf and its receptor TfR, followed by excessive iron accumulation in the body. Iron overload in the body may further lead to the death of pancreatic beta cells and insulin resistance by increasing oxidative stress, inducing iron death, interfering with the insulin signaling pathway, and causing autophagy deficiency. In addition, non-enzymatic glycation affects the binding of Tf with chromium and reduces the ability of Tf to transport chromium into tissues, resulting in a decrease in the levels of chromium in tissues and ultimately affecting the sensitivity of tissues to insulin. In diabetic patients, the concentrations of glycated Tf in serum were significantly correlated with those of fructosamine.Tf has a shorter half-life, and not affected by anemia or hypoalbuminemia and less negative charge under physiological conditions, while glycated modification could not change the isoelectric point of Tf, which easily passes through the negatively charged basement membrane of the glomerulus. Therefore, compared to glucosamine, HbA1C, etc., glycated Tf may be a future biomarker for evaluating short-term glycemic control and early renal damage in diabetic patients.

A Genetic Perspective on Diabetic Complications: A Mendelian Randomization Study on the Increased Risk of Cataracts in Type 1 Diabetes

“…Diabetes is a metabolic disease where prolonged high blood sugar levels can lead to various complications. In ophthalmology, diabetes can affect the health of the lens in multiple ways, including accelerating cataract development through promoting nonenzymatic glycation reactions and oxidative stress [16][17][18]. It's reported that the likelihood of cataracts in diabetic patients is five times higher.…”

Identification of candidate biomarkers and pathways associated with multiple sclerosis using bioinformatics and next generation sequencing data analysis

“…HK2 [269], PNPLA3 [270], CPB2 [271], SEMA4C [272], LRP2 [273], SLC5A11 [274], F11 [275], ANGPTL2 [276] and CYP2A6 [277] genes might be related to the pathophysiology of autoimmune disease. A recent study revealed that SLAMF7 [278], FCRL3 [279], CCR4 [280], GZMA (granzyme A) [281], CCR2 [282], CD48 [283], CD3E [284], CCL4 [285], FASLG (Fas ligand) [286], SLAMF1 [287], CD28 [288], IL7R [289], UBASH3A [290], CD3D [291], ICOS (inducible T cell costimulator) [292], CCL5 [293], CCL3 [294], LTF (lactotransferrin) [295], CTLA4 [296], TNFRSF9 [253], C6 [297], IL5RA [298], IL2RG [299], NPY2R [300], DRD3 [301], CD52 [302], CD163 [303], IQGAP2 [304], PRPH (peripherin) [305], MSR1 [306], HGF (hepatocyte growth factor) [307], TTR (transthyretin) [308], IL9 [309], ADM (adrenomedullin) [310], ANGPTL4 [311], CHI3L1 [312], CDH1 [313], SREBF1 [314], CDKN1C [315], TSC22D4 [316], CFTR (CF transmembrane conductance regulator) [317], INSIG1 [318], HSD17B3 [319], GREM1 [320], ATF3 [321], HK2 [322], TF (transferrin) [323], GLUL (glutamate-ammonia ligase) [324], DMRT2 [325], FN3K [326], TREH (trehalase) [327], ADAMTS4 [328], BMP2 [329], LMNA (lamin A/C) [330], ERBB3 [331], HSD11B1 [332], DLL1 [333], NKX2-2 [334], FGF11 [335], ASPA (aspartoacylase) [336], FASN (fatty acid synthase) [337], PNPLA3 [338], ADORA1 [339], WNT7A [340…”

Discovery of age-related early-stage glycated proteins based on deep quantitative serum glycated proteome analysis

“…Previous studies on serum early-glycated proteins predominantly focused on individual high-abundance proteins, such as glycated hemoglobin, glycated albumin, and glycated transferrin [ 15 , 25 , 26 ]. In contrast, our advanced proteomics platform allows for the detection of both highly abundant and low-abundance glycated proteins.…”

“…Detecting early-stage glycation is vital for early monitoring and better intervention in aging-related deterioration [10] . Some well-known early-stage glycated markers, such as glycated hemoglobin and glycated albumin, have been utilized as indicators for blood glucose control monitoring, while early-stage glycated transferrin shows potential for monitoring blood glucose control and early diagnosis of diabetic nephropathy [ 15 , 20 , 21 ]. These findings underscore the importance of studying early-stage glycated proteins in biological processes.…”