# The brain and insulin use



## NYMedic828 (Mar 14, 2012)

So I have been having an unsolvable debate with my two partners over the past couple of days on whether or not the brain NEEDS insulin in relation to being hypo or hyperglycemic.

My partners argue that when someone's sugar is through the roof, their body has no circulating insulin to facilitate it into the brain, resulting in AMS. Basically they are saying hyperglycemic AMS occurs for the same reason hypoglycemic AMS occurs. Which I argued was wrong and it is completely opposite.

My thoughts are that it is rare to have a hyperglycemic patient who is truly AMS without other symptoms of acidosis, suggesting that the brain isn't processing glucose and that the reason is because when a person is hyper their brain still utilizes the surplus of circulating glucose and the body tissues resort to burning fats and ketone bodies until eventually acidosis may set in, potentially causing AMS.

From searching google I found that the brain does not NEED insulin to utilize glucose but the presence of insulin does still facilitate the usage of glucose.

So what's the real answer here?


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## Anjel (Mar 14, 2012)

My understanding is that insulin gets the sugar into cells, brain etc.

When there is too much circulating blood sugar, there is not enough insulin, and no need for all the extra sugar.

So the body goes into overdrive to get rid of it and burn it off.

I think you are right. Any altered mental status from hypERglycemia, is secondary to another body process like DKA or whatever. Kidneys will start to shut down, and.the body becomes toxic.

Thats just my understanding. So smart people....teach


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## NYMedic828 (Mar 14, 2012)

In my classroom and self teaching I was taught that the brain is the only body tissue that functions off of serum glucose and doesn't necessarily need insulin to facilitate it the way body tissues do. Thought the presence of insulin will speed the process, the brain can function fine atleast for a significant period of Time without it.

In hypoglycemia it doesn't matter if you have insulin or not because there is not enough glucose to feed the brain as is.

The body cells can always resort to burning more fatty acids and ketone bodies but eventually that causes ketonic acidosis.


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## mikie (Mar 14, 2012)

*The technically term for -glycemia AMS*

Neuroglycopenia.

now say that 10 times fast.


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## mycrofft (Mar 14, 2012)

In hyperglycemia the body doesn't burn off excess sugar, it tries to eliminate it (through the kidneys mostly). Any "burning off" is catabolysis of fats and protein to fuel other pathways, and the toxic waste from that is  ketones etc.

If there is insufficient insulin, "the body demands" more intake in an attempt to  bring more sugar to the game. It can detect "not enough", but not "too much".



http://diabetes.diabetesjournals.org/content/51/12/3384.full

PET studies indicate insulin does affect sugar uptake in the brain. It does other things as  well


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## NYMedic828 (Mar 14, 2012)

mycrofft said:


> http://diabetes.diabetesjournals.org/content/51/12/3384.full
> 
> PET studies indicate insulin does affect sugar uptake in the brain. It does other things as  well



So the brain can function without insulin yes?


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## mycrofft (Mar 14, 2012)

Maybe in a bell jar for a little while. What do you see when a diabetic isn't given enough insulin?


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## FourLoko (Mar 14, 2012)

Timely thread. Went to pick up a frequent flyer yesterday for her 3 day per week treatment. Found her to be tachy ~115. Hadn't transported her in a while so not sure if that was normal for her.

What I did remember is her normal level of alertness (is that a word?) and she awake and responsive. Non verbal as normal, eyes tracking us and head nodding.

Long story short, the LVN finally gets in gear and checks her BGL (should have been done before we arrived) and it was 249. Could explain the tachycardia but otherwise she seemed just dandy.


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## NYMedic828 (Mar 14, 2012)

mycrofft said:


> Maybe in a bell jar for a little while. What do you see when a diabetic isn't given enough insulin?



Hyperglycemia, but usually never AMS. I was always taught that is because the brain works on serum glucose whereas the rest of the body needs insulin to make use of glucose.


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## mycrofft (Mar 14, 2012)

All glucose is transported in the bloodstream, except the part that tastes good (on the tongue) which is NOT significantly absorbed. Short chain sugars (and alcohol) can cross the blood-brain barrier. So, is glucose for the brain in serum, or in CNS?


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## NYMedic828 (Mar 14, 2012)

mycrofft said:


> All glucose is transported in the bloodstream, except the part that tastes good (on the tongue) which is NOT significantly absorbed. Short chain sugars (and alcohol) can cross the blood-brain barrier. So, is glucose for the brain in serum, or in CNS?



No idea. I know they both have sugar and I'm sure it uses it from both...

But in the absence of insulin, can the brain function normally.


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## mycrofft (Mar 14, 2012)

And again, what does someone look like who does not produce insulin and has not injected it recently?








Answer is, in the real world, no it/they cannot.


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## Veneficus (Mar 14, 2012)

*This is not going to be easy to hash out.*



NYMedic828 said:


> So I have been having an unsolvable debate with my two partners over the past couple of days on whether or not the brain NEEDS insulin in relation to being hypo or hyperglycemic.
> 
> My partners argue that when someone's sugar is through the roof, their body has no circulating insulin to facilitate it into the brain, resulting in AMS. Basically they are saying hyperglycemic AMS occurs for the same reason hypoglycemic AMS occurs. Which I argued was wrong and it is completely opposite.
> 
> ...



The glucose that the brain uses for energy is transported across the blood brain barrier by insulin independant glut 3 transporters. 

Parts of the brain do not have a blood brain barrier and insulin concentration does play a role in metabolic hormone signaling pathways. 

The whole system is quite complex and dependant on what part of the brain, intrisic energy supply vs systemic, feed/fast states and catecholamine signaling as well. 

So does the brain require insulin? No

Insulin does have numerous effects in the brain. Including IGF1 inhibition of GHRH.

The cause of AMS also has multiple causes

here is a good read that touches on the CNS complications.

http://emedicine.medscape.com/article/907111-overview#showall


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## mycrofft (Mar 14, 2012)

OK, knew you'd join soon and get it unsnarled. Do these transporters also act as the passport through the cell membranes to allow glucose to get, eventually and via no doubt tortuous pathways, to the mitochondria to produce energy?

Nevertheless, though, without insulin (or a hypothetical insulin analog) the body can no longer support the brain and we haven't got the head transplant thing quite licked yet.

Maybe next week.


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## Veneficus (Mar 14, 2012)

mycrofft said:


> OK, knew you'd join soon and get it unsnarled. Do these transporters also act as the passport through the cell membranes to allow glucose to get, eventually and via no doubt tortuous pathways, to the mitochondria to produce energy?
> 
> Nevertheless, though, without insulin (or a hypothetical insulin analog) the body can no longer support the brain and we haven't got the head transplant thing quite licked yet.
> 
> Maybe next week.



This article breaks it down by types of brain cells.

http://physiologyonline.physiology.org/content/16/2/71/T1.expansion.html

and points out that the cells that do require glut 1 transport will suffer from lack of insulin with neuro defects.

It is just more detailed than the last source i used for the glut 3. (which was a biochemistry review of insulin)


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## Christopher (Mar 14, 2012)

Just to flesh this conversation out, I think it is important to touch on the necessity of more than just insulin for glucose metabolism. Thiamine is sometimes required with alcoholics experiencing hypoglycemia (think Wernicke’s encephalopathy).

Without B1 the brain cannot feed, even with an adequate supply of glucose and insulin.


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## mycrofft (Mar 14, 2012)

In VIVO! I like it.
We used to stuff those guys with B1, BID PO, for a month if they stayed locked up that long.

Vene,  Iread the articles (don't be afraid, readers, they're short but to the point). Thanks!!


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## Christopher (Mar 14, 2012)

Another good article is a study from March 2006 Experimental Neurology which covers the translocation of GLUT3. It has pretty pictures and brings up the important role than potassium appears to play in glucose uptake by neurons.

Insulin regulates neuronal glucose uptake by promoting translocation of glucose transporter GLUT3:



> Our data demonstrate that insulin stimulated translocation of GLUT3 to the plasma membrane is not sufficient to increase glucose uptake, which is consistent with neurons being classified as insulin insensitive...Previous studies have shown that neuronal glucose uptake is markedly increased by depolarization with high extracellular K+.  In this study, insulin potentiation of glucose uptake stimulated by depolarization with KCL is likely a result of increased numbers of docked GLUT3 available for fusion with the plasma membrane. Our study suggests that neuronal glucose uptake is regulated by at least two, separable factors; promotion of GLUT3 translocation to the plasma membrane and membrane depolarization that induces fusion of GLUT3 vesicles with the plasma membrane.


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## mycrofft (Mar 14, 2012)

You know, going back to OP, this is also about altered mentation with inadequate insulin.

Ketones and pH shift are not going to help that either.


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## NYMedic828 (Mar 15, 2012)

So are these statements correct?

Hypoglycemia - The brain is very sensitive to low glucose levels and can't compensate by burning fats and ketones like other body tissues, resulting in a relatively rapid onset of AMS/Consciousnesses.

Hyperglycemia - A good portion of the brain (not all of it) can transport glucose into the cells independently of insulin and as a result, in an acute time frame the brain can compensate for a decent period of time. Usually until the buildup of ketonic acids causes a metabolic acidosis.




Also, does failure of the brain without insulin ultimately occur because the brain doesn't have insulin, or because the supporting body tissues/organ systems linked to the brain can't function without insulin?

Ultimately, both myself nor my partners are fully wrong or right. The brain is so complex that we are both right, the brain doesn't need insulin, but in the end it really does?


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## Veneficus (Mar 15, 2012)

NYMedic828 said:


> Hypoglycemia - The brain is very sensitive to low glucose levels and can't compensate by burning fats and ketones like other body tissues, resulting in a relatively rapid onset of AMS/Consciousnesses.?



The brain can use ketones as an alternative energy source. The problem is they are produced in sufficent quantities in order for them to power the brain for long.

So your answer is partially right.



NYMedic828 said:


> Hyperglycemia - A good portion of the brain (not all of it) can transport glucose into the cells independently of insulin and as a result, in an acute time frame the brain can compensate for a decent period of time. Usually until the buildup of ketonic acids causes a metabolic acidosis.



The issue is not specifically ketones, as the brain can use them. But ketones are produced by the breakdown of fatty acid, which the brain cannot do. 

The main problem with hypoglycemia is membrane (both cellular and mitochondrial) functions. (Na, K, H etc transport and permiability.)



NYMedic828 said:


> Also, does failure of the brain without insulin ultimately occur because the brain doesn't have insulin, or because the supporting body tissues/organ systems linked to the brain can't function without insulin??



Yes, for both reasons.

The Glut 1 receptors in parts of the brain require insulin, without it, they will fail.

As well, metabolic (hormonal and catecholamine) signalling alters the function of other organs. Which will fail without insulin as well as ultimately fail from inability of homeostasis trying to compensate. 



NYMedic828 said:


> Ultimately, both myself nor my partners are fully wrong or right. The brain is so complex that we are both right, the brain doesn't need insulin, but in the end it really does?



I think you will have to settle for both being pertly right and partly wrong.

The brain is a rather complex thing and 1 or 2 mloecules and biochemical processes do not accurately describe all of the interrelated functions.


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## NYMedic828 (Mar 15, 2012)

Thanks for the awesome responses.

While like you said it is extremely complex and I don't feel I have nearly the knowledge and understansing I wish I did on body systems but I definitely feel more informed now.

How some of you have such extensive knowledge is beyond me...

MD by chance?


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## Veneficus (Mar 15, 2012)

NYMedic828 said:


> Thanks for the awesome responses.
> 
> While like you said it is extremely complex and I don't feel I have nearly the knowledge and understansing I wish I did on body systems but I definitely feel more informed now.
> 
> ...



something like that


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## mycrofft (Mar 17, 2012)

Next patient!


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## Veneficus (Mar 18, 2012)

mycrofft said:


> Next patient!



Perfect.

If I thought the outfit would keep people from coming to the house seeking advice, I would go with it.

I particularly like the absence of a white coat.


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