The ratio of insulin to c-peptide, impacts how well blood vesseld dilate. Too much insulin is devastating – it causes low grade inflammation.
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The origin of that low grade inflammation
If you’re battling to control your sugar levels, then you are keen to maximize the amount of insulin doing the rounds. Because, more insulin in the circulation, will facilitate more glucose uptake, particularly by muscle cells.
But did you know insulin has a fraternal twin ?
His name is C-peptide. To understand more about…..
Insulin’s other half
We have to go back to the beginning……
“Baby” insulin, officially named proinsulin, consists of two strands, shown in red, joined together by an intermediate chain, shown in green. The bit in the middle is the middle is referred to as the connecting peptide or C-peptide for short.
An enzyme, PCSK rips off the bit in the middle, creating a mature insulin. And in the process the bit in the middle, is released, forming the C-peptide.
Both insulin and C-peptide are released from the beta cell, in response to sugar.
A piece of junk ?
Initially, it was thought that the C-peptide was just junk. But, this is biology…………….Mother Nature is not in the habit of wasting resources.
The C-peptide has been found to be biologically active.
One of the things it does, is it regulates blood flow, by acting directly on red blood cells.
Red blood cells are to all intents and purposes, bags of haemoglobin, loaded with oxygen. As the red blood cells make their way down the nooks and crannies of various organs, they donate some of the oxygen they are carrying, to oxygen starved cells.
The oxygen is moving down a concentration gradient.
And the stimulus for the oxygen to be donated is the level of carbon dioxide.
The trouble is…………….. in order to make the exchange, the red blood cells must be able to traverse through the very narrow capillary pipes.
Now the heart is helping to push them forward, up to a point. But, the push from the back is NOT enough, to force them through pipes that are often smaller than they are.
Moving through the microcirculation requires much squeezing and squishing.
Physics keeps them a ambling forward, but red blood cells help themselves too. If you want to learn a little bit more about how this happens, watch this video, it introduces the concept of the fourth phase of water.
The help yourself endeavour
Okay, okay………. helping themselves might be a stretch. When they find themselves stuck between a rock and a hard place. The screams for oxygen and the cries from behind to get moving, bring on a stress response.
The ACCIDENT causes tiny amounts of ATP to be released into the environment.
The endothelial cells don’t take too kindly to the soiling of the environment. When the ATP locks onto special receptors on their surface, they pull in their bellies. And let off a bit of a stink of their own, which ends up…..
Saving the day
The blood vessels dilate and there is more room for the red blood cells to move through. And deliver their cargo of oxygen. The myriad of nutrients dissolved in the blood, travelling alongside the red blood cells, take advantage of the expansion………..
So these oxygen deliveries facilitate grocery deliveries.
Despite being in charge of grocery deliveries, insulin interferes with this process. Eish ! This is what a team of researchers from Missouri discovered. They found as the levels of insulin increase, the amount of ATP that is released plummets.
It’s not a hundred per cent deliberate.
The ATP release depends on increases of cAMP.
You win some you lose some
Now insulin stimulates a cascade of responses inside cells and red blood cells are no exception. They have an insulin receptor and when insulin knocks on the door, the activity of the enzyme phosphodiesterase 3 is stimulated.
Unfortunately phosphodiesterase decreases cAMP. Eish !
No worries…….insulin’s twin, C-peptide, comes to the rescue. Right ?
Red blood cells are one of the cell types, that are sensitive to C-peptide. When they are exposed to increasing concentrations of C-peptide, they cause ATP to be released.
Not exactly, our team found, c-peptide also interferes with ATP release. It just doesn it, in a different way !
Oh no ! Time to hit the panic button ?
Twinning to find a solution
On paper at least, neither insulin or C-peptide, should be making the rounds alone. Remember, they’re come from the same molecule (pro-insulin) and are released together. Under normal physiological circumstances, for every insulin molecule doing the rounds, there should be one C-peptide molecule.
Together they make a fantastic team.
Provided they are in THE RIGHT ratio.
This is what our team found – when oxygen levels are normal, nothing happens, but when oxygen levels are low, ATP flows. It’s a biological win…. when the ratio of C-peptide to insulin, is just “right”.
Under normal physiological conditions, insulin’s whoopsie is taken care of by C-peptide.
Blood vessels dilate.
Oxygen and groceries are delivered.
But insulin and C-peptide are NOT two peas in pod, they’ve got VERY DIFFERENT temperaments. And this is highlighted, as they plummet into the liver and negotiate BORDER CONTROL.
The stronger twin wins
C-peptide RESISTS all attempts by the liver to capture it.
Insulin, is not quite as sly and is grabbed by the liver and suffers the consequences.
Well, this is what typically happens, in someone who is insulin sensitive.
It is estimated that somewhere between 50 to 80 % of the insulin is cleared by the liver. It’s not a bad thing, it’s normal biology.
So in the circulation, the number of C-peptides far outweighs, the number of insulin molecules.
But, in those prone to INSULIN RESISTANCE, insulin puts up a fight…..
When insulin resists
The “tough talk” and aggression, showed by the insulin molecules, as they move through the liver, is quite unexpected. The shell shocked liver, lets more insulin through into the periphery.
The amount of insulin cleared plummets.
This is reflected by hyperinsulinemia.
Now the number of C-peptides, relative to the number of insulin molecules circulating, is more equitable.
To hell in a hand basket
The more insulin molecules doing the rounds, the greater the level of phosphodiesterase enzyme stimulation, the harder it is to make sugar deliveries.
And oxygen deliveries.
The technical term for the condition is HYPOXIA.
Welcome to low grade inflammation.
So to create BETTER BODY CHEMISTRY, you MUST improve deliveries of EVERYTHING : sugar, cholesterol and oxygen.
Fixing the insulin : C-peptide ratio would be first prize, but right now, exactly how to do this, is a bit of a mystery. What we do know, is lowering the levels of insulin circulating, will definitely help…… because it will empower the liver, to clear more – thus correcting the ratio.
But you have lots of options to improve deliveries. Click here to discover 9 plus ways to do this.
NOTE : Exercise is one of the ways to do this, but it’s not on this list.
Synergistic effects of C-peptide and insulin on low O2-induced ATP release from human erythrocytes. Am J Physiol Regul Integr Comp Physiol (2013) 305: R1331–R1336. Jennifer P. Richards, Alan H. Stephenson, Mary L. Ellsworth, and Randy S. Sprague.
Low O2-induced ATP release from erythrocytes of humans with type 2 diabetes is restored by physiological ratios of C-peptide and insulin. Am J Physiol Regul Integr Comp Physiol (2014) 307: R862–R868. Jennifer P. Richards, Gina L. C. Yosten, Grant R. Kolar, Cory W. Jones, Alan H. Stephenson, Mary L. Ellsworth, and Randy S. Sprague.
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