Physiology of insulin release - know your pancreas

finsit

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This is a great read for anyone who needs to understand their diabetes and hyperglycaemia. It cleared several of my questions that I always wondered based on my experiments.

In particular the affect of GLP and incretins over the stimulation of insulin secretion was an interesting read.

https://www.pancreapedia.org/reviews/secretion-of-insulin-in-response-to-diet-and-hormones

However, I still have one question that i can not find a satisfactory answer so far, so what are your personal experiences or guestimate on it. The question is at what blood glucose level your endogenous insulin (first response) releases? I notice in my case that my BG regulation is mainly managed by my endogenous insulin (second phase response). Its only when my BG reaches close to 7 mmol that the first phase insulin gets released and i am guess it because that is the point where it goes back very quickly. However, when its in mid 6's, its always slow to go back into 5's.

Happy reading.
 
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Antje77

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The question is at what blood glucose level your bolus insulin (first response) releases? I notice in my case that my BG regulation is mainly managed by my basal insulin.
This is very confusing. The terms 'bolus' and 'basal' insulin are related to injected insulin, not to endogenous insulin.
I suppose you are talking about your own insulin response, not injected insulin, right?

If I were you, I would edit my post to prevent totally confusing answers.
Or just delete it and start a new thread.
 

Oldvatr

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About 10 mmol/l is what the IGTT test uses to ensure first phase response. When an arginine block is in place then the level is over 20 mmol/l before the pancreas releases insulin,
This is a great read for anyone who needs to understand their diabetes and hyperglycaemia. It cleared several of my questions that I always wondered based on my experiments.

In particular the affect of GLP and incretins over the stimulation of insulin secretion was an interesting read.

https://www.pancreapedia.org/reviews/secretion-of-insulin-in-response-to-diet-and-hormones

However, I still have one question that i can not find a satisfactory answer so far, so what are your personal experiences or guestimate on it. The question is at what blood glucose level your bolus insulin (first response) releases? I notice in my case that my BG regulation is mainly managed by my basal insulin. Its only when my BG reaches close to 7 mmol that the bolus gets released and i am guess it because that is the point where it goes back very quickly. However, when its in mid 6's, its always slow to go back into 5's.

Happy reading.
Thank you for posting. There is a typo in ~Table 1
Section V is of interest which is describing the voltage controlled switching that controls insulin generation and release.

Although it mentions granules, it does not make it clear that these store insulin locally in the pancreas and it is this store that is released during the First Phase insulin response. The granules hold insulin in hexameric form i.e. 6 insulins attached to a glycerol stem in the pancreas granules,

I think but am not certain, that the reason why the ND weight loss program improved the P#1` insulin response was that the granules or the messaging path got blocked off by the fatty tissue, which cleared due to the intervention. so IMO the apparent loss of P#1 response may be a storage problem in the beta cell, and this does not need the mind bending theory of beta cell de-differentiation to explain it. The solution may be quite simple.
 
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Oldvatr

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This is very confusing. The terms 'bolus' and 'basal' insulin are related to injected insulin, not to endogenous insulin.
I suppose you are talking about your own insulin response, not injected insulin, right?

If I were you, I would edit my post to prevent totally confusing answers.
Or just delete it and start a new thread.
I think Bolus is an appropriate term to describe the Phase 1 Insulin Response
"
Why is it called a bolus?
In digestion, a bolus (from Latin bolus, "ball") is a ball-like mixture of food and saliva that forms in the mouth during the process of chewing (which is largely an adaptation for plant-eating mammals)."

"Definition of basal ; of or relating to the foundation, base, or essence : fundamental ; b · of, relating to, or being essential for maintaining the fundamental .."

Tnis soft ball with saliva is actually responsible for triggering the amylase enzyme which in turn triggers the P#1 response normally in humans. The P#1 dose that results is usually capable of returning homeostasis after a meal in non diabetics. But the liver will provide support to maintain this homeostasis,, and so requires insulin to allow either storage or use of glucose in the blood supply which is a basal function.

The research paper itself uses these terms.
 
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Antje77

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I think Bolus is an appropriate term to describe the Phase 1 Insulin Response
While the terms might make sense from a linguistics point of view, it's very confusing on a forum of diabetics on insulin and diabetics not on insulin, because they're not usually used in this sense.
However, I was only trying to help finsit in getting the answers he's looking for, and it's completely his choice if he'd like to adjust his post to prevent confusion.
Let's get back on topic.
 
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Bubbleblower

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The question is at what blood glucose level your bolus insulin (first response) releases?.

"Glucose-induced β-cell electrical activity, recorded with glass microelectrodes, is characterized by trains of fast action potentials (“spikes”). The membrane depolarizes before each train of spikes and then depolarizes. This pattern is termed a “burst.” There is a characteristic biphasic response to a square wave of 11.1 mM glucose. Pulses at higher glucose concentrations (22.2 mM or more) evoke transient, constant spike activity."

Possibly this is why some schools say you should stay below 11.1 precisely (I always assumed that number came from 200mg/dl/18).

The theory of beta cell de-differentiation may be mind bending but fact is high glucose changes the alpha to beta cells ratio, which may be why it is so important to give your overworked pancreas some rest.
 

Oldvatr

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"Glucose-induced β-cell electrical activity, recorded with glass microelectrodes, is characterized by trains of fast action potentials (“spikes”). The membrane depolarizes before each train of spikes and then depolarizes. This pattern is termed a “burst.” There is a characteristic biphasic response to a square wave of 11.1 mM glucose. Pulses at higher glucose concentrations (22.2 mM or more) evoke transient, constant spike activity."

Possibly this is why some schools say you should stay below 11.1 precisely (I always assumed that number came from 200mg/dl/18).

The theory of beta cell de-differentiation may be mind bending but fact is high glucose changes the alpha to beta cells ratio, which may be why it is so important to give your overworked pancreas some rest.
I do not recognise the units you quote. (nM) Is this nanomol or nanomol/l? The first is a molecular weight, the latter is a density.

Do you have a source for the 11.1 you reference? Certainly 11.1 mmol/l is not a healthy level.

What is the source of the alpha/beta ratio? Is it post mortem, or biopsy, or from the MRI scans from the Newcastle Diet IGTT report or their application for for future funding into de-differentiation. If it is their application then it is conjecture since they have not proven their hypothesis. It is a prospective study.
 

KK123

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Thanks for posting, interesting article if a little complicated! It serves to remind us that trying to emulate all of this by estimating how much insulin to inject at any given time is somewhat tricky.
 
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finsit

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This is very confusing. The terms 'bolus' and 'basal' insulin are related to injected insulin, not to endogenous insulin.
I suppose you are talking about your own insulin response, not injected insulin, right?

If I were you, I would edit my post to prevent totally confusing answers.
Or just delete it and start a new thread.
Thanks updated with first and second phase.
 
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Oldvatr

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"Glucose-induced β-cell electrical activity, recorded with glass microelectrodes, is characterized by trains of fast action potentials (“spikes”). The membrane depolarizes before each train of spikes and then depolarizes. This pattern is termed a “burst.” There is a characteristic biphasic response to a square wave of 11.1 mM glucose. Pulses at higher glucose concentrations (22.2 mM or more) evoke transient, constant spike activity."

Possibly this is why some schools say you should stay below 11.1 precisely (I always assumed that number came from 200mg/dl/18).

The theory of beta cell de-differentiation may be mind bending but fact is high glucose changes the alpha to beta cells ratio, which may be why it is so important to give your overworked pancreas some rest.
According to the papers i reviewed, the output of insulin is indeed pulsative. but the period of oscillation is around 15 minutes for non diabetics, but diabetics do tend to be faster ( but in the range 5 to 15 minutes per pulse period. So the term 'fast pulse train' is perhaps misleading.
 

Mr_Pot

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This is a great read for anyone who needs to understand their diabetes and hyperglycaemia. It cleared several of my questions that I always wondered based on my experiments.

In particular the affect of GLP and incretins over the stimulation of insulin secretion was an interesting read.

https://www.pancreapedia.org/reviews/secretion-of-insulin-in-response-to-diet-and-hormones

However, I still have one question that i can not find a satisfactory answer so far, so what are your personal experiences or guestimate on it. The question is at what blood glucose level your endogenous insulin (first response) releases? I notice in my case that my BG regulation is mainly managed by my endogenous insulin (second phase response). Its only when my BG reaches close to 7 mmol that the first phase insulin gets released and i am guess it because that is the point where it goes back very quickly. However, when its in mid 6's, its always slow to go back into 5's.

Happy reading.
Thanks for that, lots of interesting information which will take me a long time to study properly. I did note in a quick scan that amino acids and fatty acids also result in an increase in Insulin but I haven't had time to find out why.
 

Oldvatr

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Thanks for that, lots of interesting information which will take me a long time to study properly. I did note in a quick scan that amino acids and fatty acids also result in an increase in Insulin but I haven't had time to find out why.
lipid storage requires insulin to open the gates similar to storing glycogen.
 

finsit

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Thanks for that, lots of interesting information which will take me a long time to study properly. I did note in a quick scan that amino acids and fatty acids also result in an increase in Insulin but I haven't had time to find out why.
Yes, its well known that proteins do spike Insulin that is why in keto diet they don't recommend high proteins as it kicks them out of ketosis. Per Dr. Bernstein, 36% of protein converts to sugar.
 

Bubbleblower

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What is the source of the alpha/beta ratio? Is it post mortem, or biopsy
The sources are both from biopsy and post mortem and I also have an interesting study that found alpha/beta ratio in type 2 diabetics was exactly twice as high as in those with normal glucose tolerance. And very very important; the alpha/beta ratio correlates with diabetes duration!

But this is all of topic.

How about reducing the alpha to beta ratio instead?
 

Oldvatr

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Bubbleblower

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“In conclusion, the pancreatic α/β increased after type 2 diabetes onset and correlated with diabetes duration, while relative alpha-cell area correlated with HbA1c.”
Human Pancreatic Alpha- to Beta-Cell Area Ratio Increases After Type 2 Diabetes Onset

"We observed an eight times increased frequency of insulin cells coexpressing glucagon in donors with diabetes." Loss of β-Cell Identity Occurs in Type 2 Diabetes and Is Associated With Islet Amyloid Deposits

I wonder what explains these different outcomes, but I am not gonna break my head over it now.
 

Bubbleblower

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The study in post #16 states: "In some of these studies, alpha cell mass could be calculated and was reported to be decreased by about 45% [16], unchanged [15] or increased by 40–80% [4, 17]." so there is a lot of potential for cherry picking.

In conclusion, the following report is an analysis of beta cell dysfunction which is relevant to the dedifferentiation discussion, but not the OP
https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC4010577/

Nice study, I completely agree with:
"there are good reasons to think that obtaining euglycemia with treatment will restore the normal phenotype of these β cells" which is what I base my strategy on even though it's not real science according to the opinion leaders on this forum. Despite that it sure seems to be working.
 
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Erin

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This is a great read for anyone who needs to understand their diabetes and hyperglycaemia. It cleared several of my questions that I always wondered based on my experiments.

In particular the affect of GLP and incretins over the stimulation of insulin secretion was an interesting read.

https://www.pancreapedia.org/reviews/secretion-of-insulin-in-response-to-diet-and-hormones

However, I still have one question that i can not find a satisfactory answer so far, so what are your personal experiences or guestimate on it. The question is at what blood glucose level your endogenous insulin (first response) releases? I notice in my case that my BG regulation is mainly managed by my endogenous insulin (second phase response). Its only when my BG reaches close to 7 mmol that the first phase insulin gets released and i am guess it because that is the point where it goes back very quickly. However, when its in mid 6's, its always slow to go back into 5's.

Happy reading.


cool - thank you