Wherefor Insulin

[colubridae]

I have always been puzzled by one aspect of insulin.

Why?

If I understand the biology:-

Glucose passes from the gut into the bloodstream.
It circulates in blood plasma where it reaches the pancreas
Islet of Langerhans cells detect glucose via receptors on the beta cells.
Insulin is then released
It circulates in background levels and in surge-mode when glucose levels are high.
It attaches to receptors which activate GLUTS (transporters) for facilitated diffusion into cells. Where it is needed.


Why did evolution develop such an unnecessary system?

Why not have glucose transporters activated directly by the receptors (on beta cells) on cells where glucose is needed (I think that’s all cells).

(I do understand that insulin and ILGF have other functions besides glucose uptake, but this doesn’t explain the extra (unnecessary) layer of control)


Is this another example of the pointlessness one would expect from natural selection but not from intelligent design?

Like the laying of optic nerves in front of the rods and cones in the retina.


Hope this question makes sense.
Any answer would be welcome.

[mistermack]

Is this another example of the pointlessness one would expect from natural selection but not from intelligent design?

Like the laying of optic nerves in front of the rods and cones in the retina.


Hope this question makes sense.
Any answer would be welcome.

Well yes, you have supplied the answer there, but it's only pointless from a designer point of view. The existing system is there, all the mechanisms are there to produce it in the offspring, and unhelpful faults have died out over millions of years.

The question makes sense, but it's the wrong question really. But many people who know a lot more than me still ask it.
If you look at evolution as a struggle between individuals, it leads you to think that way.
You really have to look at it as a struggle for survival of GENES.
Evolution doesn't look for better solutions, it doesn't look for anything. Genes either survive and multiply, or die out.
Although we think of creatures as superbly adapted to their environment, you could spend years of your life pointing out better solutions, you would never run out of candidates.
The one that mystifies me is : why don't prey animals develop better night sight, like cats? The answer is always the same. The genes that would have brought that about have never prospered. They have to survive and prosper in every individual that passes them on. New characteristics start with a mutated gene.
To develop a better system for handling glucose, that mutation has to interact with all the established genes perfectly, has to reproduce perfectly, AND has to out-compete long-established genes.
And on top of that, it probably needs many other mutations to enable the system, and they all have similar challenges. They have to survive and multiply long before the advantage of better glucose regulation comes into being. Each mutation needs it's own advantages all along the way.

So the boiled down answer is : The genes never made it, the existing genes won.
.

[Xamonas Chegwé]

Pretty much nailed it, MM. As Richard Dawkins puts it, "You can't get to a higher point on mount improbable by going downwards first." In other words, EVERY mutation must either be as good as, or at least no worse, than what already exists. If it requires a dozen separate mutations to achieve a better overall system, ALL of them must meet that criteria - otherwise, they will be quickly weeded out.

[pcCoder]

But how do you define 'worse'? Surely it would be possible though probably not likely for some members of a population to develop genetic variations that would decrease fitness from an evolutionary stance, but not to a point of no reproduction at all, just a slight decrease in reproduction and survival, and still some of the offspring of those members may develop genetic variations that may work in conjunction with previous variations that would increase fitness beyond the initial fitness, which would not do so without that previous variations that decreased fitness.

[mistermack]

Who needs a meaning anyway, I'd settle anyday for a very fine view.
Sandy Denny

I'd settle for hearing Sandy Denny singing again.
.

[Xamonas Chegwé]

But how do you define 'worse'? Surely it would be possible though probably not likely for some members of a population to develop genetic variations that would decrease fitness from an evolutionary stance, but not to a point of no reproduction at all, just a slight decrease in reproduction and survival, and still some of the offspring of those members may develop genetic variations that may work in conjunction with previous variations that would increase fitness beyond the initial fitness, which would not do so without that previous variations that decreased fitness.

In evolutionary terms, 'worse' means 'less able to survive long enough to reproduce successfully'. If a mutation means that you are less capable of surviving, or less capable of reproducing, that gene will be weeded out over time.

The only exception is one of artificial selection, which would require a conscious effort - such as the breeding of turkeys so that they can now only reproduce by AI!! When vertebrates were developing pancreases, endocrine systems and all that goes with them, there was no selection around except for natural selection - which is a cruel, harsh, blind and unforgiving master (unless you listen to the ID crowd, of course. )

[colubridae]

Many thanks for reply.

Don’t get me wrong I am a fully paid-up card-carrying selfish.gene/ext.phenotype/memetics believer (actually I hope we are headed down the Asimov C/Fe/Si route).

My point was ‘Is the extra loop in the negative feedback necessary?’ or is it just another ox-bow cut off by the clumsy meanderings of natural selection.

My intention is to use insulin as another argument against creationism and I didn’t want the argument to blow up in my face, because of a missed detail making insulin/glucagon an ‘engineering’ necessity. I couldn’t see any, but as I’m sure you have noticed by now I am often wrong.

From your answer I take it you wholeheartedly agree it is a classic natural selection ‘mistake’.

Do you have any other human examples of such.

I would also be interested in your take on meiotic drive as a mechanism for neaderthal extinction.

The one that mystifies me is : why don't prey animals develop better night sight, like cats? The answer is always the same. The genes that would have brought that about have never prospered.

“Law of diminishing returns” , surprised you are mystified.

They have to survive and prosper in every individual that passes them on.

No.

New characteristics start with a mutated gene.

Surprised you think that.

To develop a better system for handling glucose, that mutation has to interact with all the established genes perfectly, has to reproduce perfectly, AND has to out-compete long-established genes.

Yes of course, except the ‘perfectly’ bit.

They have to survive and multiply long before the advantage of better glucose regulation comes into being.

No. If the ludicrously unlikely statistical event occurred, the advantage would be immediate. That’s not to say the advantage would de facto ‘take’ in the population.

Each mutation needs it's own advantages all along the way.

No.

p.s. better glucose regulation is not the problem. The same required glucose regulation at much lower cost – i.e. no langerhans cells. (I include the glucagon leg in the developed discussion of course).

Pps My set text for evolution was Futuyma.

[ficklefiend]

As the body is made, in my head the insulin/glucagon control creates that steady swing between hypo/hyper glucose- necessery due to the fact that we tend to eat sporadically?

If the cells were directly influenced by the presence of glucose, perhaps the delivery of this would be in favour of more "hungry" cells at the detriment of keeping a regulated level of glucose for the brain to use? Afterall, apart from the brain other sources of energy can be utilised.

The rub is that some of these problems could be overcome in much the same way that the problems whith using insulin are overcome- in areas where there are high levels of insulin, the pancreas, there are less receptors on the cells, so that these cells do not get an unfair amount of glucose uptake. A similar system could happen all over the body, if you were to re-design it from scratch.

As you can see, I'm only working off basic biochemistry here. Please feel free to crush my ramblings, I'm sure you will.

[colubridae]

As the body is made, in my head the insulin/glucagon control creates that steady swing between hypo/hyper glucose- necessery due to the fact that we tend to eat sporadically?

If the cells were directly influenced by the presence of glucose, perhaps the delivery of this would be in favour of more "hungry" cells at the detriment of keeping a regulated level of glucose for the brain to use? Afterall, apart from the brain other sources of energy can be utilised.

The rub is that some of these problems could be overcome in much the same way that the problems whith using insulin are overcome- in areas where there are high levels of insulin, the pancreas, there are less receptors on the cells, so that these cells do not get an unfair amount of glucose uptake. A similar system could happen all over the body, if you were to re-design it from scratch.

As you can see, I'm only working off basic biochemistry here. Please feel free to crush my ramblings, I'm sure you will.

Not at all the question has vexed me for many years.

My basic point is that whatever the control mechanism is (and I can appreciate the need for one) it doesn't need the extra complication of insulin/glucagon

The rub is that some of these problems could be overcome in much the same way that the problems whith using insulin are overcome- in areas where there are high levels of insulin, the pancreas, there are less receptors on the cells, so that these cells do not get an unfair amount of glucose uptake. A similar system could happen all over the body, if you were to re-design it from scratch.

That’s my point in a nutshell. An intelligent designer would certainly have not gone to the trouble of installing an extra component viz insulin/glucagon.


Another intriguing question is what accident set natsel off in that wasteful direction in the first place.
Insulin/glucagon is highly conserved so it’s been in use for a long time. Whatever caused it happened a long while back.

[colubridae]

What really fucks with my head is knowing that the genes for the glucose transporters used by the langerhans cells exist in every cell in the body (erythrocytes excluded of course).

Whatever switch activates the insulin receptors only needs to patch over to langerhans GLUT and Robert is your mother’s brother.

Just a single switch away from being embedded in the surface of every cell that needs glucose.

Not such a climb down and up mount probable after all.

As usual I cannot grasp the missing jig-saw piece. ‘The devil’s in the detail’. Little bastard.

[Gawdzilla Sama]

What really fucks with my head is knowing that the genes for the glucose transporters used by the langerhans cells exist in every cell in the body (erythrocytes excluded of course).

Whatever switch activates the insulin receptors only needs to patch over to langerhans GLUT and Robert is your mother’s brother.

Just a single switch away from being embedded in the surface of every cell that needs glucose.

Not such a climb down and up mount probable after all.

As usual I cannot grasp the missing jig-saw piece. ‘The devil’s in the detail’. Little bastard.

Think "unintended consequences". Sickle-cell anemia, for example.

[colubridae]

What really fucks with my head is knowing that the genes for the glucose transporters used by the langerhans cells exist in every cell in the body (erythrocytes excluded of course).

Whatever switch activates the insulin receptors only needs to patch over to langerhans GLUT and Robert is your mother’s brother.

Just a single switch away from being embedded in the surface of every cell that needs glucose.

Not such a climb down and up mount probable after all.

As usual I cannot grasp the missing jig-saw piece. ‘The devil’s in the detail’. Little bastard.

Think "unintended consequences". Sickle-cell anemia, for example.

If you mean insulin has other functions, definitely.
Otherwise I'm not sure what your point is. Can you elaborate please...

This is a model of the insulin molecule in my kitchen... I think I need to get out more...

100_9315.JPG

[mistermack]

Hi, I don't know if I can be all that much help. Having an interest doesn't make me an expert.
Firstly, I would comment that it's not the best choice for a debate. Very few people will understand the finer points of glucose handling, me included, so you would have to debate it with and in front of some very clued up people. I prefer the sickle cell anaemia example, or even things like the vestigial tails and appendix etc. Another favourite of mine is the fact that our sexual lubricants smell exactly like the lubricant that covers many fish, after a few hours in the air.

As far as why it hasn't evolved as you suggest it should/could, it's something that people will be arguing about just as much in a hundred years' time.
Just because we can infer a lot from fossils, it's tempting to think we can predict what should happen. But it's much harder to write a book, than to read one.
Evolution is incredibly unpredictable, especially when it comes to higher animals.
You can perhaps predict that bacteria or viruses will evolve immunity to drugs, but it's much harder to successfully predict how higher species will evolve.
The only one that comes to mind is the preponderance of tuskless elephants, following the ivory blitz, but I can't think of any others.

I think the answer is probably that the change that you imagine could be brought about by one single mutation, would in reality require many many more than that.
Once you're into more than one mutation, it becomes much more unlikely, because the first one has to 'stick', and out-compete the existing gene, to stand a cat-in-hell's chance of being there when the next required mutation takes place.
One mutation on it's own could produce a sickly individual, that wouldn't thrive, or be neutral, and never really spread.
If all that was required was one mutation, and a less complicated system of glucose handling was there working perfectly, then I agree it would and should have happened by now.

On the extinction of the Neanderthals, I haven't heard of any work on meiotic drive being involved, I wouldn't mind some references to have a look at.

My own FEELING is that Neanderthals were very sedentary people, intimately involved in their territory, and specialising in exploiting local features, like places where herds of migrating game got concentrated. I've read this opinion on several occasions, contrasting them to modern humans, who seemed to have the capacity to 'up sticks' and adapt to circumstances.
This would make Neanderthals very vulnerable to climate change, and their demise seems to coincide with the last ice age.
It's not just the ice that was a killer, it was the drastic climate change that travelled in front of the ice.
So when modern humans started spreading out from the middle east, the Neanderthals were probably down to just a few pockets anyway, and probably just couldn't cope with the competition.

[colubridae]

Hi, I don't know if I can be all that much help. Having an interest doesn't make me an expert.
Firstly, I would comment that it's not the best choice for a debate. Very few people will understand the finer points of glucose handling, me included, so you would have to debate it with and in front of some very clued up people. I prefer the sickle cell anaemia example, or even things like the vestigial tails and appendix etc. Another favourite of mine is the fact that our sexual lubricants smell exactly like the lubricant that covers many fish, after a few hours in the air.

Ok my apologies, as usual my assumptions got the better of me. I assumed that from what you said on the other thread you were an expert.

This is my simple insulin analogy

‘You live in a house, where the electricity supply is intermittent.
One lamp is left plugged in. When it lights you know the juice is on.
You send someone round to plug-in the fridge, the freezer, the central heating etc.
These plugs pop out after a while. But you keep sending the plugger-in round the house.
When the lamp goes out, you stop sending the plugger-in round the house’

Cock-a-mammy or what?

A single hox gene change could swap receptors from insulin to glucose. Whilst there are undoubtedly a ‘chain’ of genes involved somewhere along the line is a gene which says ‘this receptor is for insulin’. Change that gene to glucose receptor and you get glucose receptors, yes I’m oversimplifying, but it’s definitely not a complete system rebuild.
I believe in the words of the prophet dawkins ‘DNA is a recipe not a blueprint’
I may be wrong, but I think that is the case.

Given that, I would have expected, an alternative evolutionary pathway to have been traced. This leaves the ‘bug me’ question ‘What goes on in the control of glucose that makes insulin/glucagon feedback a seeming necessity?’
Most of natsel works through energy budgeting. Could the islet cells be doing complex maths (making them more expensive) to produce a proportionate response to glucose in the bloodstream?
Are the GLUTs on islet cells significantly more expensive than insulin GLUTs?

Your point about this not being suitable place for debate astounds me. Doesn’t stop people arguing about electrons being photons. Call me crazy but you seemed quite happy to engage in a far more difficult debate on electron structure.
<== colubridae

On the extinction of the Neanderthals, I haven't heard of any work on meiotic drive being involved, I wouldn't mind some references to have a look at.

I’m pretty sure you won’t find any references, It’s me spitballing.
It started on RDF. I engaged a theist twerp on the epicurean dilemma. He evaded the issue and I added the Neanderthals. Along the lines of "Why did skydaddy make the Neanderthals extinct? Evidence suggests they were gentler, more intelligent creatures yet they got the chop without being given a chance to develop”


After more baloney from him, I put the idea of segregation distorters as an extinction mechanism for them. He pointed me to creationist website bullshitting about god’s meiotic drive. Naturally for me I went ballistic and hounded him to my own extinction. Go with that for the irony.


If segregation distorters got them, there would be a single clear evidential signature. Whether it would show up in the fossil/archaeological evidence I don’t know. I’m not privy to Neanderthal dig results.


If you like, we can continue the same ethics discussion as I started on RDF, but without the god twaddle.

My own FEELING is that Neanderthals were very sedentary people, intimately involved in their territory, and specialising in exploiting local features, like places where herds of migrating game got concentrated. I've read this opinion on several occasions, contrasting them to modern humans, who seemed to have the capacity to 'up sticks' and adapt to circumstances.
This would make Neanderthals very vulnerable to climate change, and their demise seems to coincide with the last ice age.
It's not just the ice that was a killer, it was the drastic climate change that travelled in front of the ice.
So when modern humans started spreading out from the middle east, the Neanderthals were probably down to just a few pockets anyway, and probably just couldn't cope with the competition.

Yeah sorry I was hoping for more than a wiki condensate. My apologies for the incorrect assumption.

As they say ‘I makes an ass out of u & me’

[mistermack]

Ok my apologies, as usual my assumptions got the better of me. I assumed that from what you said on the other thread you were an expert.

Nope, I'm just very interested in human evolution, and used to debate it regularly on the Dawkins site.
Twiglet accused me of being farsight's 'sock puppet', so I wrote :

Twiglet, don't waste your time. I know nothing about farsight, and not much past A level phyics. My real interest is human evolution, but I enjoy the concepts of physics.

I was really just making it clear I had no connection with farsight, and was actually more interested in human evolution.
.....................
The analogue of the house and plugs is a good picture, I can see what you're getting at.
How far back does insulin go? Do fish use the same system? Or invertebrates?

Your point about this not being suitable place for debate astounds me.

I'm not sure we're on the same wavelength there. I was saying it's not a great choice of subject, to debate with creationists, in front of a non-scientific audience. That's why I said they would need to be clued up to follow it. If the real debating point is 'is there a designer?, you need a simpler subject, to keep peoples' minds on the point.
It just depends who you are debating with, and who is following it.

Yeah sorry I was hoping for more than a wiki condensate. My apologies for the incorrect assumption.

I don't know what wiki says on that score. What I wrote is just about where my opinion ended up after several debates on Dawkins.
I think the real mystery of the Neanderthals is why there seems to have been no interbreeding with modern humans. I think it was that that caused their extinction. If interbreeding didn't happen, extinction of one or the other was pretty inevitable, given our warlike nature.
Find out what prevented interbreeding, and you find out what killed the Neanderthals.
.