A Hyperglycemic condition in diabetes promotes formation of advanced glycation end products, which are known to elicit immune response and form complexes with immunoglobulins called circulating immune complexes. To investigate the involvement of advanced glycation end product (AGE)-modified proteins in the elicitation of an immune response, circulating immune complexes were isolated and proteins associated were identified and characterized. Label-free-based mass spectrometric analysis of circulating immune complexes in clinical plasma of prediabetic, newly diagnosed diabetes, and diabetic microalbuminurea revealed elevated levels of serum albumin in the circulating immune complexes, which were also observed to be AGE modified. Further, to examine the role of glycation, circulating immune complexes were analyzed in the streptozotocin-induced diabetic mice treated with or without aminoguanidine, a prototype glycation inhibitor. Mass spectrometric analysis of circulating immune complexes showed elevated levels of serum albumin in plasma from diabetic mice over that of control animals. Aminoguanidine-treated diabetic mice displayed decreased AGE modification of plasma albumin, accompanied by a reduced level of albumin in the circulating immune complexes. In addition, elevated levels of proinflammatory cytokines such as IL-1b, IL-2, and TNF-alpha were observed in diabetes, which were reduced with aminoguanidine treatment, suggesting the involvement of glycation in the immune response.

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The advanced glycated end products (AGEs) are formed in the diabetic patients; it is a major cause of macrovascular and microvascular complications in diabetes. Clinically there is no treatment available for the AGEs. Stveoside (Stv), a sweetener has potent anti-diabetic and anti-oxidant activity. Hence, we investigated its use in prevention of AGEs formation using in vitro and in vivo models. Diabetes was induced by streptozotocin (STZ). These rats were kept without treatment till blood HbA1c was markedly increased. They were then divided into 5 groups and treated orally with vehicle or Metformin (MET) or Stv respectively for 28 days. Every 7th day, animals were tested for body weight and blood glucose (BG). On the last day of treatment, all the groups were evaluated for physiological and biochemical parameters, histopathology and AGEs; N-carboxymethyl-lysine (CML) estimation. Stv showed inhibition of AGEs in in vitro as well as in in vivo respectively. Positive effects were seen on the BG, lipid profile and urine parameters as well it showed reduced formation of CML. It also showed antihyperglycaemic, antihyperlipedemic and nephroprotective activities. The present study provides scientific rationale for the use of Stv as a sweetener with additional benefits in diabetes.

Background: Alzheimer’s disease (AD) is the most common form of dementia and about two thirds cases are diagnosed late due to a long asymptomatic phase. There exists the need for newer biomarkers which can add accuracy to AD diagnosis, detect AD at an early stage, as also lend new pathogenic insights into AD. Recent AD biomarker discovery has focused on proteomic approaches, especially in the cerebrospinal fluid. Methods: We used a bottom-up proteomic approach. Cerebrospinal fluid (CSF) samples from 6 patients with AD and 6 controls were digested with trypsin and analyzed by using LC-MS/MS (tandem mass spectrometry). The peptide data from CSF samples of both AD and control groups was then subjected to bioinformatics analysis with STRING version 11.0. Protein-protein interaction networks were constructed, and enrichment analysis performed.Results: Significant up-regulation of 13 proteins in the CSF was observed in AD cases in comparison to controls, while 30 proteins were down-regulated. APOE and LGALS3BP were the upregulated proteins involved in closed network and the downregulated proteins were F2, PENK, IGF2, APOH, SAA1, AHSG, SPP1 and CD44. APOE, APOH, F2 and PENK shared common involvement in multiple biological processes as evident on enrichment. Regulation of insulin like growth factor involving IGF2, F2, APOE and AHSG and glycosaminoglycan binding involving APOE, APOH, F2, SAA1, and CD44 were major pathways of interest determined on bioinformatic analysis.Conclusion: Our study identified novel tentative biomarkers of AD which included F2, PENK and SAA1, as well as reinforced earlier described biomarkers such as APOE and AHSG. These findings need to be validated in larger sample sizes to evaluate their utility as true biomarkers. Further, the pathways of interest- insulin like growth factor regulation and glycosaminoglycan binding need to be studied further in the context of AD.

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