Further, all GLP-1 constructs inhibited in vitro T cell migration, suggesting direct immune-modulatory actions. Lecture 31 - Periodate Cleavage, Retrosynthesis, and Green Chemistry Overview. All experiments were approved by the government of North Rhine-Westphalia, Germany. glucose tolerance test (C) (B: n = 5–7/group, one-way ANOVA; and C: n = 5/group, two-way ANOVA). To investigate whether this immune-regulatory effect of GLP-1 and its cleavage products was restricted to the kidney or also present systemically, we performed FACS analysis of blood and heart tissue. All animals were fed a high-fat Western-type diet (39 kJ% fat, 41 kJ% carbohydrates, and 20 kJ% protein [ssniff EF R/M acc. 4I). In this reagent, the periodate group is protected, as it were, by four acyl groups in the cyclic structure shown below. The oxidative cleavage with periodic acid has been succesfully applied in the constitutional analysis of sugars. Acetate is a weak nucleophile, but in this case it is strong enough to extract a proton. Blood leukocytes (7-AAD−, CD45+) were gated for T-helper cells (TCRβ+ NK1.1−, CD4+), cytotoxic T cells (TCRβ+ NK1.1−, CD8+), and monocytes (Ly6G−, CD11bhigh, CD115+). Write the structure of the reactant. Further, GLP-1 constructs had no effects on glomerular podocyte damage as detected by podocin or synaptopodin expression (Fig. 2G). Zygmunt Marczenko, Maria Balcerzak, in Analytical Spectroscopy Library, 2000. Dilute the sample solution containing not more than 300 ug of Mn, free from chloride and other reducing agents, in a beaker, with water to about 15 ml. The method has been applied to the determination of ribonucleosides158, but the risk of photochemical disturbances is a limitation48. Flow cytometric analysis was performed on an FACS LSR-Fortessa running FACS Diva 8.0.1 (BD Biosciences) and analyzed with FlowJo (Tree Star). [23][24], Periodate cleavage may be performed on an industrial scale to form dialdehyde starch which has uses in paper production.[25]. A. Hassner, I. Namboothiri, in Organic Syntheses Based on Name Reactions (Third Edition), 2012. Proceed further as described above. Buffy coats were obtained completely anonymized from the Department of Transfusion Medicine, University Hospital RWTH Aachen, which does not require ethical approval in Germany. As to the mechanism, it is illustrated here. GLP-1 (9-36 amide) and GLP-1 (28-36 amide) have been found to exhibit GLP-1 receptor-independent properties, which include inhibition of weight gain, improvement of glucose metabolism, and reduction of oxidative stress (15–17). 2C, E, and F). 2A) 48 h postreperfusion. 1A–C) or serum electrolytes (Supplementary Fig. P.B. [-Arg-Gly], C-term. is the guarantor of this work and, as such, had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. At extremes of pH additional species can form. Importantly, the GLP-1 receptor agonists liraglutide and semaglutide, which mimic the peptide structure of GLP-1, were found to improve cardiovascular and renal outcome and reduce cardiovascular and overall mortality in high-risk patients with diabetes (2,3). 4E) while not affecting Ly6C-low MoMFs (Supplementary Fig. In the db/db experiment, for renal and cardiac tissue, live cells (Hoechst negative) were gated by the following strategy: T-helper cells were CD45 positive, CD19 negative, and CD4 positive; cytotoxic T cells were CD45 positive, CD19 negative, and CD8 positive; macrophages were CD45 positive, Ly6G negative, and F4/80 positive cells. To further investigate the mechanisms of renoprotection, we treated a human tubular cortical cell line (HK-2) and a murine renal tubular cell line in addition to primary human T cells under in vitro conditions with GLP-1 and its cleavage products. To further characterize the immune-modulatory actions of GLP-1 and its cleavage products under in vivo conditions, we used the unilateral renal I/R injury mouse model. No other potential conflicts of interest relevant to this article were reported. M.L. Nitric acid solution, boil 1 litre of 0.2 N nitric acid with approximately 0.1 g of potassium periodate, allow to cool and store in an all-glass wash-bottle. The presence of several pairs of vicinal diols such as those in glucose during oxidation with $\ce{HIO4}$ can … This has been explained in terms of dative bonds, confirming the absence of double bonding in these molecules. In conclusion, we found GLP-1 and its cleavage products GLP-1 (9-37) and GLP-1 (28-37) to have glucose-independent renoprotective effects. Further pharmacological judgment of the renoprotective potential of GLP-1 cleavage products will require head-to-head comparison with renin-angiotensin-aldosterone system-blocking agents and/or SGLT2 inhibitors. ə d eɪ t / is an anion composed of iodine and oxygen.It is one of a number of oxyanions of iodine and is the highest in the series, with iodine existing in oxidation state +7. Periodic acid attacks the vicinal diols in carbohydrates and oxidizes these groups to form carbonyl compounds. ; ABS 046-03; Dianova) and anti-Glp-1 (midmolecule specific; HYB 147-12B; Dianova). 4F). Glucagon-like peptide 1 (GLP-1) is an incretin hormone secreted by intestinal L cells and pancreatic α-cells (1). [14][15] The most common example of this is diol cleavage, which was also the first to be discovered (Malaprade reaction). 1B and C). To investigate metabolic, renal, and cardiac effects of GLP-1 and its cleavage products, we overexpressed DPP-4-resistant GLP-1 (7-37 Mut8) and two GLP-1 cleavage products, GLP-1 (9-37) and GLP-1 (28-37), in db/db mice on a high-fat diet using an AAV vector system. Copyright © 2020 Elsevier B.V. or its licensors or contributors. 3A). Measure the absorbance of the solution at 528 nm against water or a reagent blank. This was not associated with a differential expression of the renal tubular injury marker Lcn2 or histological assessment of tubular injury (Supplementary Fig. Recent clinical trials have demonstrated marked differences in cardiovascular outcomes among available incretin-based therapies in patients with diabetes.

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