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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.
We feature the endothelial nitric oxide system
In someone who is insulin resistant, there is a chronic shortage of nitric oxide inside the blood vessels.
Now, nitric oxide is a colourless gas, made from an oxygen and nitrogen molecule, joined together. It’s produced by nearly every cell type.
It’s super power is it’s small and nimble, but it’s NOT very stable, it only lasts a few seconds, but that’s long enough to do some important chemistry, both inside the cell that made is, as well as, the cells in the neighbourhood.
The nitric oxide that is AWOL, is the nitric oxide produced by endothelial cells, these are the cells that line blood vessels, big ones and little ones. The endothelial cells produce nitric oxide, with the help of an enzyme, known as endothelial nitric oxide synthetase, or eNOS for short.
This nitric oxide signals to the muscle cells, surrounding the blood vessels, to RELAX.
This process of relaxing, is called vasodilation,
it allows blood to flow through effortlessly and this facilitates deliveries.
When the nitric oxide is “missing”, the blood vessels are taut, because vasoconstriction is occurring. This makes it hard for insulin to make deliveries. And when sugar isn’t delivered – sugar levels spike, causing all sorts of NEW TROUBLES.
So why is the nitric oxide NOT THERE ?
Well, on paper, it should be…..
Insulin’s job, is to put away the groceries. And grocery deliveries, need to made to every nook and cranny, within the body. But getting to every nook and cranny, takes a bit of co-ordination – insulin makes the arrangements.
You see, when the body is just “chilling”, resources are not wasted, delivering huge volumes of blood, to every nook and cranny, it is not necessary.
The cells have all the resources they need to be happy.
But, when it’s time to deliver the groceries, the story changes. At this point in time, all the vessels NEED to be open.
A little help from a friend
To get these vessels open, insulin enlists the help of eNOS.
eNOS is always sitting on the surface of the cells that line the blood vessels. He typically, just hangs out, in the caveola, attached to, a very fancy comfy “chair”, called a caveolin-1.
When eNOS, gets the nod from insulin, via calmodulin. He hops off the scaffold protein, hooks up with a partner, and together they grab electrons from NADPH, passed them to the arginine, to create nitric oxide and L-citrulline.
The nitric oxide then diffuses through the membrane to do it’s thing, at the vascular smooth muscle, it acts on the metal centre of the heme protein, cyclic GMP, causing muscle relaxation. Some of the nitric oxide, also drifts towards the caveolin-1, where it fluffs up the pillow, inviting eNOS, to stop his production of nitric oxide and relax a little.
A little R&R
eNOS, doesn’t need a second invitation and takes a break.
The status quo returns, until, the next call for a puff of nitric oxide.
Well, this is what should happen. But, when you’re insulin resistant, insulin levels are high – morning, noon and night, and this means that eNOS is firing up nitric oxide production, like a wild thing.
eNOS the wild thing
Unfortunately, when eNOS, doesn’t get down time, he get’s a little cranky and CARELESS.
The result, instead of pairing up with a friend, he opts to do his chemistry solo. The electrons from NADPH, don’t always get passed in a carefully controlled manner to arginine, instead they get tossed onto oxygen, creating peroxynitrite.
Peroxynitrite is a sizziling hot, free radical.
As it bounces around, it creates waves of destruction, within endothelial cells, leaving them unable to do their job.
Blocks, breaks and bung ups
Follow and deliveries aren’t made.
Now, this causes distress to the organs, they’re servicing.
Cells around the body go “ hungry” – they’re short of oxygen and fuel and the undelivered nutrients become problematic. Sugar, cholesterol, triglycerides – you name it, all accumulate. In addition to this, the endothelial cells, undergo changes to their permeability and structure. And platelets, becoming clutchy. Etc, etc, etc.
Compounding the problems, further.
At this point, you’re a heart attack waiting to happen
So, if you’re insulin resistant, you want to boost nitric oxide availability. There are quite a few ways to do this….
A welcome vacation
The first thing to work on, is the BAD BODY CHEMISTRY, upsetting eNOS. You can give eNOS, some much needed R&R, by reining in insulin levels. For tips and strategies, on how to do this, download our willpower report, it’s free.
In addition to this, you can put your eNOS, on a training schedule.
eNOS in training
It turns out, endothelaial cells produce nitric oxide, in response to stimulation by shear stress. And shear stress happens, anytime you get the blood moving.
A vigorous bout of exercise, is a great way to charge up your nitric oxide battery.
If vigorous exercise is out of the question, there are alternative options, that will give you some of these benefits. One of the easiest and safest is remote ischemic pre-conditioning. Click here, to learn more.
You can also, generate nitric oxide, by exploiting an alternative nitric oxide generating systems, the so-called nitrate-nitrite-nitric oxide pathway.
This system can be triggered by diet and lifestyle.
One unexpected lifestyle factor, which influences this pathway, is whether you use mouth wash. Click here, to read why, you might want to ditch that mouth wash, if you’re insulin resistant.
Being in the NO, will help your create BETTER BODY CHEMISTRY and better health.
Nitric oxide is just one of hundreds of chemicals in the body that are amiss, when you’re suffering from metabolic syndrome, click here, to discover more “players”.
Vascular nitric oxide: Beyond eNOS. Journal of Pharmacological Sciences 129 (2015) 83e94. Yingzi Zhao, Paul M. Vanhoutte, Susan W.S. Leung
Regulation of obesity and insulin resistance by nitric oxide. Free Radic Biol Med. (2014) 73:383-99. Brian E. Sansbury and Bradford G. Hill
Metabolic Effects of Dietary Nitrate in Health and Disease. Cell Metab (2018) 28(1):9-22. Jon O Lundberg, Mattias Carlström, Eddie Weitzberg.
When you’re insulin resistant, sugar can’t leave the blood, because the glucose gates, normally used by the sugar molecules, are missing. Gate moving needs…
When skeletal muscles, know insulin is coming, they move their GLUT4 gates from the periphery to front and centre, with the gates in place, glucose gets in.
When a heart attack strikes, the nitric oxide battery is the key to calming the panic and getting oxygen to the tissue minimizing damage. To charge your battery – move.