Is insulin that the pancreas produces all the same?

[rebrascora]

Just been pondering this question a bit recently...

Obviously those of us on MDI have 2 different insulins, basal and bolus, whereas people on a pump just use small doses of quick acting insulin for basal as well as bolus. My question is, does the latter better replicate the natural action of a pancreas (I am guessing it does) or does the pancreas produce different types of insulin for different purposes, OR does the pancreas possibly have different beta cells that are responsible for producing the same insulin but for different purposes.... ie some which produce a steady trickle to cover basal and others which are stimulated when food is eaten. Or could it be that the immune system damages them in some cases where they can still manage a steady trickle but not ramp up production of insulin for food.
The reason I ask is that people's basal requirements can vary enormously and I wondered if there were possibly different beta cells that produced insulin for different purposes, then could some remain relatively intact whilst others, perhaps the food ones which may have been under more strain, be more vulnerable in some cases?

Just curious really as to why basal requirements can vary to such a very large extent although I appreciate most people fall within a reasonable range. I understand that body mass and metabolism play a part but just wondering how it all works.

 

[Inka]

As far as I understand, a working pancreas just produces one kind of insulin and pushes out tiny amounts throughout the day and night, then larger amounts to control blood sugar when you eat.

So, yes, a pump most closely mimics it because it only has the fast-acting insulin and pumps out minuscule amounts (as basal) every few minutes with larger amounts when you bolus for meals.

 

[Inka]

The long-acting basal insulins were originally ‘normal’ insulin with things added to slow down their action, I think.

(And were, of course, animal-derived originally)

 

[mikeyB]

Indeed, Beta cells and insulin are the same throughout the animal kingdom. It’s a curiously persistent molecule throughout evolution, which is how animal insulins could be used in humans and work just as well. Cows and pigs were the original source, but you could use elephant or whale, cat or dog. It’s just what’s socially acceptable.

I take Creon capsules with meals because my pancreas no longer produces sufficient digestive enzymes. The enzymes in Creon are extracted from pig pancreas. Good job modern insulins are made from bacteria and yeasts, more pigs left for us Creonistas. And, of course, carnivores like me. (Pork joint in the freezer).

 

[rebrascora]

Really fascinating that it is the same in all creatures.... there must be a boat load in that whale that washed up in Essex!

I too am partial to a pork shoulder or chop and I think we both have a guilty pleasure in their skin.... I am sure I have heard mention of pork scratchings being on your shopping list too!

 

[trophywench]

Shame they've stopped selling - decent ones in such a lot of pubs now. Mind you, dunno if my teeth are missing them so much recently!

 

[everydayupsanddowns]

I have seen a conference presentation which said that us PWD are attempting to manage while delivering the wrong insulin into the wrong place at the wrong time. Which I quite liked!

 

[trophywench]

I like that Mike - just TG we all still can at the moment!

 

[leonS]

Insulin is made of two chains of aneno acids cross linked by sulphide bonds. Such bonds are weak, which is why insulin would be destroyed by the digestive acid if taken by mouth.

It is not the same for all amimals! Pig insulin differes by five ameno acids, and cow by seven (if memory serves!), although in most animals some form is made and it does the same job.

Originally we were injected with ground up pig pancreas, refered to by Banting and Best as "muck". Early efforts were directed at imptoving the purity by removing unwanted matter.

The action of insulin was changed by the addition of heavy metals to make it longer acting. Short acting insuin was still used and was called "soluable".

Modern insulin is man made and long acting insulin is produced by making changes to the molecule.

While a pump is much closer to the natural system the method of delivery is different. The pancreace puts insulin directly into the blood a pump under the skin. This slows the action. Too, there is no autonatic control as with a working pancreace.

 

[mikeyB]

Those animal amino acid differences make little or no difference to the effectiveness in humans. The body doesn’t recognise the difference.

However, the thought occurs to me that badly designed as we humans are, maybe our bodies are used to an older pre-human insulin, which differs in some degree to our current version. That might account for why so many humans become insulin resistant, or why in T1s the immune system reacts to destroy its production. For sure, that would account for the genetic link in both types.

In Europeans around 2-4% of our DNA is Neanderthal. In Africans there is none. In the East, and Polynesian populations or their descendants (Maoris, Australian Aborigines, Native Americans) they have no Neanderthal genes but between 3-6% Denisovan. In Africans there is none. Only African folk are pure human. So is there a difference in the structure of insulin between these populations? There’s certainly a huge difference in the frequency of our autoimmune conditions. And other illnesses too - the Inuit folk, another part Denisovan population, eat huge amounts of saturated fat- they eat Beluga whale blubber raw - because it’s their only source of Vitamin C. They don’t fur up their arteries.

It’s those Neanderthal genes that’s killing us. Did for them, too. But is there a difference in the human insulins around the world? Has anyone looked?

 

[Inka]

That’s a fascinating idea @mikeyB 😎 I’ve never heard of anyone looking into that. Years ago I read something about the emergence of insulin resistance in Northerly populations but I’ve never read anything as specific as Neanderthal genes.

I think there was a study about the prevalence of Type 1 around the world that showed how the risk could increase if people from a low-prevalence group moved to a high-prevalence country. I’d love to know more about things like that.

 

[leonS]

Those animal amino acid differences make little or no difference to the effectiveness in humans. The body doesn’t recognise the difference.

However, the thought occurs to me that badly designed as we humans are, maybe our bodies are used to an older pre-human insulin, which differs in some degree to our current version. That might account for why so many humans become insulin resistant, or why in T1s the immune system reacts to destroy its production. For sure, that would account for the genetic link in both types.

In Europeans around 2-4% of our DNA is Neanderthal. In Africans there is none. In the East, and Polynesian populations or their descendants (Maoris, Australian Aborigines, Native Americans) they have no Neanderthal genes but between 3-6% Denisovan. In Africans there is none. Only African folk are pure human. So is there a difference in the structure of insulin between these populations? There’s certainly a huge difference in the frequency of our autoimmune conditions. And other illnesses too - the Inuit folk, another part Denisovan population, eat huge amounts of saturated fat- they eat Beluga whale blubber raw - because it’s their only source of Vitamin C. They don’t fur up their arteries.

It’s those Neanderthal genes that’s killing us. Did for them, too. But is there a difference in the human insulins around the world? Has anyone looked?

The Neanderthal part of me dictates that I point out that I never suggested that the differenge in insulins made any difference to its action. Having used insulin intended for pigs for 30 years or so, I can report that it works rather well in humans, or at least in this one.

BUT no one can be certain that the difference is not inportent. The difference might account, in some part for the long term problems that type 1s face and are usually atributed to poor control. As we no longer need to use animal insulin this is not likely to be the subject of research.

It may turn out that changing the insulin molecule to make it long acting will cause problems in 50 years, but I am certain that I shall not be around to see this.

I do not think that a change in the insulin molecule has anything to do with the body distroying the means of production. There are numerous examples of where things just go wrong: cancer, alergy, breathing and heart problems are all examples

 

[mikeyB]

All of which are less common in those with a Denisovan inheritance...