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When you’re insulin resistant, that is, you’ve got metabolic syndrome, pretty much every chemical in the body is NOT QUITE RIGHT. Some are up. Some are down. Few are actually at physiologically NORMAL levels.
Traditionally the focus is on the big guns.
- And cholesterol
In this series, we take a look at some of the other players.
Who they are, what they’re up to and how they’re part of the state of insulin resistance.
In this post, we feature AGEs
(advanced glycation end-products)
In someone who is insulin resistant, the AGE-RAGE alarm is going off, unabated. Constantly living in a state of ANGST, puts the immune system in a state of perpetual readiness.
And a trigger happy immune system – can cause collateral damage.
The situation manifests, as low grade inflammation and is synonymous with BAD BODY CHEMISTRY.
Triggering the alarm
It all starts with AGEs, they are the “eye soar” that hits the panic button.
AGEs are NOT a biological phenomenon.
There formation happens SPONTANEOUSLY, when a sugar and an amino acid, rub shoulders. The caboom, that follows, forms a Schiff base and this is highly unstable molecule. It can fall apart, allowing the sugar and the protein, to part company, unscathed by the encounter.
Or, a water molecule can pop on, facilitating a re-arrangement of the atoms, to form an Amadori product. At this stage, it is still possible for that water molecule to fall off, and the protein and sugar to part company, but more often than not, the atoms, get locked down, into an extremely stable form.
NOTE : HbA1c, the marker of glycemic control, is an example of an Amadori product.
Reactive carbonyl species
The problem with amadori products, is the longer they hang around, the higher the odds, that they undergo a chemical rearrangement and in the process, become a REACTIVE carbonyl species.
REACTIVE, they zoot around like crazy, attaching onto proteins.
It is this form, that is an advanced glycation end product or AGE for short. Now they’re not one chemical, they’re a family of chemicals. And trouble with a capital T.
First off, AGEs are an eye soar…….
Ugly and Dangerous
Plus, AGEs interfere with the normal functioning of any protein, it’s on.
This is especially problematic, when the proteins are structural proteins, because you don’t make new ones, on a daily basis. Bone, tendon, skin, blood vessels, all of these are particularly vulnerable.
In the case of blood vessels, AGEs make the blood vessels STIFF. Stiffness in the arteries, leads to high blood pressure etc.
Sugar is an AGE catalyst
Now pimples are normal, but since sugar is the flame that sparks AGE formation – the more sugar that is around, the more AGEs will be formed. In diabetics, high sugar is a permanent feature. Diabetics are given meds, to try to keep the sugar levels down, so AGE formation is minimized.
But, you don’t have a formal diagnosis of diabetes, to run into trouble.
When you’re insulin resistant, your insulin response is SLOWER, than normal – which can contribute to sugar spikes. Any time sugar levels spike, even if it is just for an hour or two, after downing a can of Coke, AGE formation is accelerated. Eish !
When pimples pop up
From a cell’s perspective AGEs are AWFUL. So when a cell realizes it has, one or more of these blemishes on it’s surface, it goes into a panic, dealing with the “pimple” becomes the priority.
The cell has quite a few tools, at it’s disposal :
- It can swallow them up and destroy them,
- it can pick them off and drop them back into the circulation, relying on the kidney to clean up
- it could try to rehabilitate them with the help of enzymes
- it could GO CRAZY and POP IT !
Surprise, surprise – the pop it strategy is the one the causes the ANGST.
The pimple popper
Cells pop their AGE pimples, with RAGEs, these are the receptor for advanced glycation end products. Cells have them, fixed to their surface and they reach over and “take care” of the problem.
Gripping the AGE tightly and THEN giving them a GOOD SQUEEZE.
This, activates the inflammatory transcription factor NFKB and in two ticks, the cell is spitting out pro-inflammatory cytokines and the situation is taken care of. And things return to normal.
Well this is what is supposed to happen…
A pimple explosion
When cells start popping pimples, left, right and centre – low grade inflammation follows…
The excess inflammation which causes collateral damage, contributing to AGEing and this, then makes you, more insulin resistant.
Which creates more sugar spikes.
It’s a vicious cycle…..
So, if you’re insulin resistant, you want to minimize triggering of AGE-RAGE axis.
The place to start, is to keep those sugar levels down inside the BODY. For tips and strategies on how to do this, download the WILLPOWER REPORT, it’s free. But, in addition to addressing the body chemistry, it’s also helpful, to minimize AGEs coming from outside, into the body.
The imported AGES
Remember I said, AGE formation had nothing to do with biology, it has to do with chemistry. Well if you bring a sugar and a protein, close to one another, cabooms happen.
So food is a souce of AGEs.
So is cigarette smoking, but that’s a another story for, another day.
NOTE : AGES in food, are not called AGES, they’re called Maillard reaction products. And they make food taste good.
It is estimated, that around 10 to 30 % of the AGEs we consume, make it, into the circulation. Now, these AGEs are probably not as dangerous, as the homemade ones, but they do matter, because, they require resources, to be allocated to their clean up.
And if they’re not cleaned up, they can initiate the inflammatory cascade. Ouch !
So the body has a plan B….
SRAGEs to the rescue
It turns out, there is a circulating version of the pimple popper – it’s referred to as soluble RAGE, just like the cell bound version, it’s programmed to seek out AGEs. And when it grabs them, it holds on tight.
A “pimple” locked down, by a SAGE, is one less pimple to worry about.
The bonus, the sRAGE has no tail – so it cannot instigate the inflammation cascade.
Unfortunately sRAGEs are a finite resource……
So, when you’re insulin resistant, you want to spare those sRAGES – one way to do this, is to eat less AGEs. Both, rodent and humans studies, suggest, low AGE diets, are helpful.
So how do you lower the AGE content of your diet ?
Eating less AGEs
Well to begin with all foods come with AGEs, some have more than others. However your cooking strategies, can make a BIG difference, to the AGE content of your dinner.
Nuking food, at a high temperature, ALWAYS ups the AGE content significantly.
Unfortunately, this is how much of our food is made today.
We eat FAST and we COOK fast.
But, it’s not how it was done in the past. We often hear about how beneficial the Mediterranean diet is and then work at, eating the same ingredients, but what’s sometimes missed, is how the ingredients are cooked, is part of the Mediterranean diet magic.
So dial down the AGE-RAGE axis, by cooking like an Italian mamma….
- lower temperatures, for a longer period of time,
- use wet cooking techniques and
- use acidic solutions, to cook with.
This will help to suppress the generation of new AGES in food and help you create BETTER BODY CHEMISTRY and BETTER HEALTH.
Uric acid, is just one of hundreds of chemicals in the body that are amiss, if you’re suffering from metabolic syndrome. Click here, to visit the “Ups and Downs of insulin resistance” page, to learn more about some of the other players.
The Role of Advanced Glycation End-products in the Etiology of Insulin Resistance and Diabetes. US Endocrinology (2010) 6:14–9. Helen Vlassara and Gary E Striker
Circulating soluble RAGE isoforms are attenuated in obese, impaired-glucose tolerant individuals and are associated with the development of type 2 diabetes. Am J Physiol Endocrinol Metab (2017) 313: E631–E640. Edwin R. Miranda, Vikram S. Somal, Jacob T. Mey, Brian K. Blackburn, Edward Wang, Sarah Farabi, X Kristian Karstoft, Ciaran E. Fealy, Sangeeta Kashyap, X John P. Kirwan, Laurie Quinn, Thomas P. J. Solomon, and X Jacob M. Haus.
AGE–RAGE Stress, Stressors, and Anti-stressors in Health and Disease. Int J Angiol (2018)27:1–12. Kailash Prasad, Manish Mishra.
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