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Carnosine in insulin resistance

Posted by Dr Sandy on in IR | 302 Views | Leave a response

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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.

  • Sugar
  • Insulin
  • 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.

Carnosine when you’re insulin resistant

Carnosine levels are down, specifically in type II fiber, predominant muscles, in someone with metabolic problems.

This problem does not happen in type 1 diabetics, implicating insulin in the process

Carnosine chemistry

The chemical name for carnosine is ?-alanyl-L-histidine.  It’s a histidine dipeptide i.e. it is a tiny molecule, made up of two amino acids, L-histidine and beta-alanine, joined together.

making carnosine

It’s not the only histidine dipeptide, there are others, but it’s the one, WE HUMANS use.

The amino acids are stuck together, by an enzyme, called carnosine synthase.

Muscles are full of carnosine.

The other place, chock full of the stuff, is the olfactory bulb, these are the nerves that smell things. But, quite a few other cell types, can and do, make carnosine, including the kidneys, where the carnosine is nephro-protective.

The carnosine bomber

Carnosine is NOT found in your blood, except immediately after dinner,  because we have an enzyme, serum carnosinase, which pulls it apart.

The presence of this enzyme, makes us, rather special.

serum carnosinase

Rats and mice don’t have it.   This means, studies done in rats and mice, might not always, be relevant for humans.

Now, when it comes to this enzyme……. there are differences.

The life and times of carnosinase

  • Some people don’t have it, at all……………..this mutation, lands them in heaps of trouble.  Carnosinemia (carnosine in the blood), is associated with mental retardation.
  • Some people are blessed with a “slow” version of the enzyme, they’re more likely to be great power athletes  and less likely to suffer from nerphropathy, should they become diabetic.

NOTE : Carnosine is the kidney is nephro-protective, i.e. it protects the kidneys.

How active your carosinase is, doesn’t just depend on genes, your body chemistry, changes the enzyme’s behaviour.  Unfortunately, high sugar levels, get it going, which is probably one of the reasons, hyperglycemia, goes hand in hand, with kidney troubles.

Carnosine is a nutrient

Now despite the presence of a carnosine bomber, we do still get some from out diet.

When we eat muscle meats, we can tap into the animal’s carnosine supplies.

the uptake of dietary carnosine

Directly, or indirectly, because muscle cells are able to take up the raw ingredients and put them back together as carnosine.

So what does the carnosine do, inside the muscle ?

Carnosine the muscle maximizer

It does quite a few things………

the benefits of carnosine inside muscle

One of the things it does, is to buffer the pH.

Exercising muscles generate protons.  This acid interferes with their function.  The imidizaole ring on the carnosine, is able to mop up the hydrogen ions.  This keeps the pH, in a comfortable range, so muscles can keep going for longer.

the pH buffering effect of carnosine

Now, this is important,  proton stress is an issue, for all muscles, muscles plagued by metabolic issues, are no exception.  In fact, they’re probably a little more vulnerable, to proton stress, but the pH buffering effect, is not the reason, carnosine is making an appearance on the ups and downs, of insulin resistance series.

Numerous studies, suggest, supplementing with canosine, can improve glycemic control.

And better sugar control, is central to BETTER BODY CHEMISTRY.

So, how does carnosine do this ?

Carnosine improves glycemic control

Well to be honest,  no one knows for sure, but one of the suggestions, is, it acts as a local histidine reservoir.  Since histidine is an essential amino acid i.e. you cannot make it, this is most helpful.

What happens, is when muscles contract, they end up pushing carnosine out.

blood vessel histidine reservoir

The carnosinase, quickly swoops in, creating L-histidine and beta-alanine.   The beta-alanine, just hangs around, but the L-histidine, is  subject to a decarboxylation reaction.

The carboxyl group, is pulled off – creating histamine.

The histamine, then hops on histamine receptors, that are on the blood vessels, running through the muscles.

The histamine hit

In response, the blood vessels, dilate.

histamine induced vasodilation

Whoohoo……………… this improves supplies, to the exercising muscle.

Muscles get

  • More oxygen,.
  • More insulin – this makes you more insulin sensitive
  • More sugar.

And you get better glycemic control.

Which is why, if you’re insulin resistant,  getting carnosine levels, up, is going  to be helpful.  And, it’s really easy to do…

Load up with carnosine

The natural approach is to eat it, by eating “muscle” i.e.  animal protein,  on a regular basis.  Red meat, chicken, fish, it doesn’t matter – they’ve all got histidine dipeptides in them, although they don’t always have carnosine.

Or failing this, consider taking a beta alanine supplement.

Supplementing for more carnosine

Why beta alanine, not carnosine ? Remember the carnosinase “bomber” – in two twos, the carnosine will be L-histidine and beta alanine.  It turns out, muscles decide how much carnosine to make, based on how much beta alanine is around.

So sending more of this in, is optimal.

The good news, you don’t have to do it for long.

Current guidelines, suggest athletes, wanting to boost their sporting performance, take 500 mg for 4 weeks. That’s enough to get the levels, high enough to make a difference.

Beware of too much

You do want to be careful, don’t take too much, in one go.   A “nasty” side effect, of big doses of beta alanine, is tingling skin (paraesthesia).  It only, happens when you take a big amount, all in one go.

So  if you’re insulin resistant,  get those  carnosine levels up – it’s help you muscles keep going, by mopping up protons and improving deliveries.

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Carnosine  is just one of hundreds of chemicals in the body that are amiss when you’re suffering from metabolic syndrome.    To learn more about some of the other players, go to our “Ups and Downs” of Insulin Resistance series.

Here are a few of the journal articles I’ve used to tell the carnosine story.

Physiology and pathophysiology of carnosine.  Physiol Rev (2013)  93: 1803–1845. Alexander A. Boldyrev, Giancarlo Aldini, and Wim Derave

Reduced muscle carnosine content in type 2, but not in type 1  diabetic patients. Amino Acids (2012) 43:21–24. Bruno Gualano, Inge Everaert, Sanne Stegen,  Guilherme Giannini Artioli, Youri Taes, Hamilton Roschel, Eric Achten, Maria Concepcio´n Otaduy, Antonio Herbert Lancha Junior,  Roger Harris, Wim Derave

Comparative physiology investigations support a role for histidine-containing dipeptides in intracellular acid–base regulation of skeletal muscle. Comp Biochem Phys (2019) 234:77-86. Eimear Dolan, Bryan Saunders, Roger Charles Harris, Jose Eduardo Pereira Wilken Bicudo, David John Bishop, Craig Sale, Bruno Gualano

The Intriguing Role of Histamine in Exercise Responses. Exerc Sport Sci Rev. (2017) 45(1): 16–23.  Meredith J. Luttrell and John R. Halliwill

Can the Skeletal Muscle Carnosine  Response to Beta-Alanine  Supplementation Be Optimized? Frontiers in Nutrition (2019) vol 6 article 135. Pedro Perim, Felipe Miguel Marticorena, Felipe Ribeir, Gabriel Barreto, Nathan Gobbi, Chad Kerksick, Eimear Dolan and Bryan Saunders

L-Carnosine supplementation attenuated fasting glucose, triglycerides, advanced glycation end products and tumor necrosis factor alpha levels in patients with type 2 diabetes: A double-blind placebo-controlled randomized clinical trial. Nutr Res. (2018) 49:96-106.  Shiva Houjeghan1, Sorayya Kheirouri, Esmaeil Faraji,Mohammad Asghari Jafarabadi.

Further reading

 

the chicken or the egg

Metabolic syndrome is not a fat thing, it’s a muscle thing

Teens with metabolic syndrome, that are not obese are slightly muscle deficient. Obese teens also have low muscle mass – suggesting metabolic syndrome is a muscle thing

insulin struggling to open blood vessel

Could a little bump on a blood vessel be the reason you’re insulin resistant ?

Insulin needs wide blood vessels to work, but widening blood vessels causes blood pressure to drop – the carotid body, keeps things in balance. Hopefully.

 

epithelial cell trying to deliver insulin

Is insulin resistance a delivery problem, not a hearing problem ?

In the insulin resistant, its thought that insulin arrives at the cell’s glucose gate, but the gate doesn’t open. What if insulin never makes it to the gate ?

 

Want to discover more ways to create BETTER BODY CHEMISTRY ?

Posted in IR | Tagged animal protein, anserine, beta-alanine, blood vessels, carnosinase, carnosine, histamine, histidine, insulin resistance, metabolic syndrome, muscle, vasodilation

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