Does glycine function as an AR inhibitor? Does it suppress endogenous fructose production?

It occurred to me to start looking for a relationship between glycine supplementation and the polyol pathway, specifically whether glycine might have some relationship to the activity of aldose reductase (AR). This enzyme (together with fructokinase KHK) appears to be at the center of events related to obesity, oxidative stress, chronic inflammation, etc. Turning it off interrupts inflammatory signaling and the response to endotoxins, but it also disrupts the breakdown of certain toxins. Its inhibition therefore may not always be desirable.

And it seems to me that I have found a certain connection between glycine and AR. It is a rather innocent-looking cataract study in diabetic rats from 2019. The authors apparently had the same idea: what if glycine interacts with aldose reductase? And they tested it in diabetic rats. And it worked!

The study was conducted in such a way that at a certain point the rats’ pancreas was chemically damaged, so insulin production stopped. This leads to an immediate increase in blood glucose levels followed by gradual organ damage. This study focused on damage to the eye lens in the form of cataracts and examined the possibility of suppressing this damage by supplementing glycine in the diet. Two levels of supplementation were used (250 and 500 mg/kg, groups III and IV), each as a single oral dose daily for 45 days. Group I is a non-diabetic control, group II is a diabetic control, and group V is a control with AR blocked using the most common pharmaceutical AR blocker, sorbinil.

I have mentioned the amino acid glycine here many times already; for example, here I described how it reduces the formation of aldehydes from omega-6 polyunsaturated fatty acids and how it suppresses the formation of advanced glycation end products (AGEs). The mechanism is still somewhat unclear; it is assumed that the basic effect is that glycine, as a building block, helps with the formation of glutathione (GSH). It thus improves antioxidant protection. However, this mechanism seems to me to be only auxiliary; the core of the effects must lie elsewhere. It is probably more complicated.

For example, precisely in the rat cataract study we can compare glycine supplementation (groups III and IV) with direct AR blockage using sorbinil (group V). And the results are very comparable. It therefore appears that the mechanism could indeed be AR inhibition. It can be seen that even this alone is able to restore GSH levels, but it also changes glucose levels and insulin production. There must therefore have been partial regeneration of pancreatic beta cells. In the groups receiving glycine, the onset of cataracts is significantly delayed. This is most likely due to suppression of AR activity in the lens epithelium. High glucose levels increase AR activity, but glycine deactivates AR. Could some intermediate of glycine metabolism perhaps serve as an AR blocker? What AR blockers do we know that contain glycine? Yes, such compounds do exist, for example Tolrestat (N-methylglycine). It is an effective inhibitor, but whether some similarly effective molecule is produced naturally during glycine supplementation, we do not know. The important thing is that it works.

We can also look at the results of an older study from 2012 with a very similar focus. The preventive effects of glycine against the development of cataracts are, in my opinion, clearly visible. The study was longer, lasting 12 weeks, and included four groups: non-diabetic control (N), diabetic control (D), diabetes plus glycine (DG), and non-diabetic with glycine (NG).

Glycine as a suppressor of the polyol pathway and oxidative stress can, together with acetate, quite substantially help correct metabolism disrupted, for example, by the aldehyde 4-HNE—that is, aldehydes formed by peroxidation of seed oils, primarily from omega-6 linoleic acid. This is a very important finding; now it just remains to verify it in a human population and put it into practice, right?


Previous

Next


References:

Protective effect of glycine in streptozotocin-induced diabetic cataract through aldose reductase inhibitory activity

Glycine therapy inhibits the progression of cataract in streptozotocin-induced diabetic rats

In Search of Differential Inhibitors of Aldose Reductase


Comments

Post a Comment

Popular posts from this blog

How to eat less and not be hungry with the help of glucose!

Image
I know it sounds strange, but not all sugars are the same. I’ll try to summarize my proposal for an easy way to lose weight without starving yourself or overexercising, using D-glucose (dextrose).  To understand how this diet system works, check out my older posts on overeating. In the first one, I explain why rats overeat by up to 50% when their diet changes . In my last post, I discuss why sucrose (regular sugar) could — but no longer can — be used to boost metabolism and raise body temperature in the distant past .   To put it briefly, based on my analysis of these studies, I’ve concluded that hunger is controlled (in a still-unknown way) by the liver — specifically, by liver glycogen levels. If liver glycogen is sufficiently high before bedtime, it means we’ve eaten enough during the day and don’t feel the need to eat more. But if it’s low, hunger forces us to eat something at night to replenish glycogen stores. The entire problem of obesity, then, lies in the broken...
Read more

Vinegar/sodium acetate rejuvenates blood vessels, another elixir of youth?

Image
In my previous post , I pointed out a study in which scientists extended the lifespan of mice by up to five months, about 17%, through mechanical stress induced by ultrasound. I also mentioned that it would be beneficial to combine the therapy with the supplementation of sodium acetate or vinegar, as these activate the same pathways, namely SIRT1 and AMPK . Immediately afterward, I came across a study showing the successful suppression of cellular senescence using sodium acetate in vascular endothelial cell cultures — the inner lining of blood vessels. Almost as if on cue, the study was published just a few days ago, on May 12th of this year. This is a fascinating study that combines the investigation of substances produced by gut bacteria that damage our blood vessels and accelerate the aging of the inner vascular lining. Researchers identified the compounds phenylacetic acid (PAA) and phenylacetylglutamine (PAGln), which are primarily produced by bacteria of the genus Clostridium. T...
Read more

How exactly do omega-6 oils affect metabolism? Is vinegar/acetate really the culprit?

Image
Let me start with some reasoning because there’s still a lot of confusion surrounding the metabolism of seed-based vegetable oils, which primarily contain the omega-6 fatty acid linoleic acid (LA). Studies show very mixed results, which is why irreconcilable camps of supporters and opponents of seed oils have formed among different dietary preference groups. You already know my stance, but I always try to remain as unbiased as possible first. This post is meant as a hard blow to researchers because everything might be completely different from what we’ve thought so far. The reason is that our researchers often forget to measure some basic metabolic parameters, which then secretly skew the results in one direction or another far more than the observed variables. But more on that later. A while back, I explained that when linoleic acid is burned in the mitochondria, there’s an increased consumption of NADPH molecules because the enzyme 2,4-dienoyl-CoA reductase (DECR) is activated. I ne...
Read more