Abundance matters: role of albumin in diabetes, a proteomics perspective

Abstract

Human serum albumin (HSA) is a multifaceted protein with vital physiological functions. It is the most abundant plasma protein with inherent capability to bind to diverse ligands, and thus susceptible to various post-translational modifications (PTMs) which alter its structure and functions. One such PTM is glycation, a non-enzymatic reaction between reducing sugar and protein leading to formation of heterogeneous advanced glycation end products (AGEs). Glycated albumin (GA) concentration increases significantly in diabetes and is implicated in development of secondary complications. Areas covered: In this review, we discuss in depth, formation of GA and its consequences, approaches used for characterization and quantification of GA, milestones in GA proteomics, clinical relevance of GA as a biomarker, significance of maintaining abundant levels of albumin and future perspectives. Expert commentary: Elevated GA levels are associated with development of insulin resistance as well as secondary complications, in healthy and diabetic individuals respectively. Mass spectrometry (MS) based approaches aid in precise characterization and quantification of GA including early and advanced glycated peptides, which can be useful in prediction of the disease status. Thus GA has evolved to be one of the best candidates in the pursuit of diagnostic markers for prediction of prediabetes and diabetic complications.

Probing Protein Glycation by Chromatography and Mass Spectrometry: Analysis of Glycation Adducts

“…Indeed, it provides an effective tool for structural characterization and quantification of individual early and advanced glycation products on the levels of individual glycated amino acids [ 76 ], peptides [ 77 , 78 ], and proteins [ 79 , 80 ]. Currently, these techniques are being effectively introduced in food quality control [ 81 , 82 ] and medical diagnostics [ 83 , 84 , 85 ]. Here we provide a comprehensive review of existing chromatographic and mass spectrometric techniques used for characterization of protein glycation adducts, i.e., analytical approaches relying on the methods of amino acid analysis.…”

Albumin Abundance and Its Glycation Status Determine Hemoglobin Glycation

“…Human serum albumin (HSA) is the most abundant plasma protein and preferentially gets glycated in diabetes owing to its abundance, as well as due to large number lysine and arginine residues accessible for glycation. 17 Therefore, the effect of clinical plasma on hemoglobin glycation can be attributed to mainly albumin and its glycation, although the effect of glucose, other metabolites, and other proteins cannot be ruled out. Individual plasma obtained from healthy control and diabetic subjects was analyzed for fasting and postprandial blood glucose, HbA1c, plasma fructosamine, and albumin levels ( Table S3 ).…”

“… 16 Hence, it was proposed that maintenance of albumin levels in diabetes would be helpful to prevent the accumulation of advanced glycation end products and delay the onset of complications. 17 Despite the great significance of albumin in diabetes, it is not routinely quantified in clinical diagnostics. However, glycation of albumin and plasma proteins is quantified as total plasma fructosamine, which is used to predict HbA1c.…”

Proximal tubular epithelial cells preferentially endocytose covalently‐modified albumin compared to native albumin

“…Albumin is the most abundant protein in the circulation with a half‐life of approximately 20 days . As a consequence of its long half‐life, albumin is susceptible to covalent modification by glycation, acetylation and carbonylation, which most commonly occur at lysine residues .…”

“…Albumin is the most abundant protein in the circulation with a half‐life of approximately 20 days . As a consequence of its long half‐life, albumin is susceptible to covalent modification by glycation, acetylation and carbonylation, which most commonly occur at lysine residues . Indeed, glycation of plasma albumin is evident in both diabetic and non‐diabetic individuals, demonstrating that circulating albumin contains a mixture of native and variably modified protein.…”