The Inhibition of Advanced Glycation End Products by Carnosine and Other Natural Dipeptides to Reduce Diabetic and Age‐Related Complications

Abstract

As people age they are at a greater risk for many disorders including cardiovascular, renal, and neurodegenerative diseases, and these conditions are exacerbated by diabetes. An important cause of the maladies associated with both age and diabetes is the formation of advanced glycation end products (AGEs). AGE formation is initiated by glycation reactions between reducing sugars and free amine groups. A cascade of other reactions follows, leading to alterations in membrane function and damage to the proteome, such as protein crosslinking. Compounds that prevent these reactions are currently being researched, but peptides hold great potential as they tend to lack toxicity, are absorbed intact, are easily produced, and are cheaper than other options. Of the peptides researched, carnosine is the most promising. Research suggests that carnosine is absorbed into the plasma unaltered and intact. Carnosine has been shown to prevent AGE formations through reduction of blood glucose, prevention of early glycation, and even reversing previously formed AGEs. Other promising peptides and amino acids include β-alanine, L-histidine, homocarnosine, anserine, and glutathione. If bioactive peptides and amino acids can minimize the formation of AGEs, foods containing these peptides could be used to improve health.

An Integrated Peptidomics and In Silico Approach to Identify Novel Anti-Diabetic Peptides in Parmigiano-Reggiano Cheese

“…In particular, the tri-peptide glutathione and some γ-glutamylcysteine derivatives from aged garlic were effective AGE inhibitors [ 43 , 44 ]. Additional di-peptides containing tryptophan (NW and QW), as well as di-peptides containing histidine (carnosine, homocarnosine, and anserine) were able to inhibit protein glycation [ 44 , 45 ]. It has been speculated that the antioxidant properties of these peptides may be pivotal for the inhibitory activity [ 45 ].…”

Protective effects of dietary carnosine during in‐vitro digestion of pork differing in fat content and cooking conditions

“…Oxidized lipids and higher processing temperature are known factors that affect the rate and amount of AGEs and ALEs formation during cooking (Poulsen et al., 2013). The capacity of carnosine to inhibit the formation of AGEs and ALEs has been reviewed (Freund et al., 2018; Ghodsi, 2019) in line with its capacity to scavenge ROS, inhibit glycation through its reaction with reducing sugars or with unsaturated aldehydic lipid oxidation products, and reverse through “transglycation” the early reaction between glucose and protein. In addition to prevent further degradation of the glycated protein, carnosine can also block the AGEs‐induced cross‐linking.…”

“…(2017) and Freund et al. (2018), respectively. Here, we are reporting for the first time that a 25% increase in free carnosine in ground pork significantly reduced protein carbonyls, loss of free thiols and 4‐HNE during in‐vitro gastric digestion irrespective of fat and cooking level of the meat, and reduced hexanal, MDA and CML up to the duodenum phase in moderately cooked lean pork.…”

The Role of Glycation on the Aggregation Properties of IAPP

“…Amongst the possible products of MGO-induced glycation is the formation of argpyrimidine, caused by reaction to arginine residues and the lysine-derived AGE produces Nε-carboxymethyl-lysine (CML) and Nε(1-carboxyethyl) lysine (CEL) (Rabbani and Thornalley, 2008;Gkogkolou and Bohm, 2012;Freund et al, 2018). Argpyrimidine is the only of the AGE products with fluorescence at 370-550 nm wavelength upon excitation at 340 nm, following a procedure previously described (Praveen et al, 2011;Beisswenger et al, 2012).…”