The brain and insulin use

[NYMedic828]

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?

 

[Anjel]

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

 

[NYMedic828]

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.

 

[mikie]

The technically term for -glycemia AMS

Neuroglycopenia.

now say that 10 times fast.

 

[mycrofft]

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

 

[NYMedic828]

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?

 

[mycrofft]

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

 

[FourLoko]

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.

 

[NYMedic828]

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.

 

[mycrofft]

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?

 

[NYMedic828]

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.

 

[mycrofft]

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.

 

[Veneficus]

This is not going to be easy to hash out.

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?

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

 

[mycrofft]

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.

 

[Veneficus]

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)

 

[Christopher]

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.

 

[mycrofft]

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!!

 

[Christopher]

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.

 

[mycrofft]

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.

 

[NYMedic828]

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?