Phase 1 insulin response

Mr_Pot said:

This has an indirect reference..
https://www.sciencedirect.com/science/article/abs/pii/S0065323308601436
Within many β granules, grains can be seen that almost certainly contain zinc insulin hexamers packed in a crystalline array

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I think the words "almost certainly" show that the proof for this statement is still in the future. It has not been proven.

It is normal to describe granules in the beta cells, but no one seems to have has shown that they contain hexamers with zinc, although that would seem to be viable since external insulin used to be made into crystalline form by combining it with zinc to slow down the reaction once injected. No one seems to have got any ESM pictures of the internal granules or a spectrometer / xray microscopy of the contents to show that humans have hexamers with zinc or a crystalline structure.

That said, it does not surprise me if our beta cells do have some local storage facility to provide a fast response to the sugar spike in the first phase response. Maybe T2D suffer a zinc deficiency that stops this from occurring? Is that why T2D lose the first response ability?

Found another paper that too is a descriptive document of the insulin hexamers, and the list of referenced sources does seem to show some nuclear resonance crystallography has taken place, so it may provide sufficient proof. However, all these papers are behind paywalls, and I have neither the time nor the inclination to go any deeper. Crystals in my urine trouble me. but in my pancreas? I can live with that.
https://link.springer.com/article/10.1007/s10534-005-3685-y

ert said:

I hope you are being referred for further investigations. As you are not on diabetic medication, then your medical team need to also consider the causes of non-diabetic hypoglycemia.

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I will fall about laughing at the idea of my chances of getting referred for further investigation.

lucylocket61 said:

I will fall about laughing at the idea of my chances of getting referred for further investigation.

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If you have an idea about how long it took me to get a true diagnosis, then during this pandemic it will be harder but insist to your GP about seeing a specialist that has the experience to get the necessary tests done.
If you are getting episodes of hypoglycaemia and you have the readings down in a food diary, show him how often it is happening.
It might not be Hypoglycaemia, but if your health team can't recognise that hypoglycaemia is involved should be able to get scans done, blood panel tests and the diagnostic tests necessary.
You need a specialist!

I know what phase one insulin response can cause, and if offered meds, to solve the problem, that is what you must do.
You have done great to get here (without the hypos) and this is a new phase in your life. And of course you must discover the source of it.
Keep on at your health care team, if you are continually annoying them wioth appointments. Eventually they must do the right thing.

I have had to wait for a specialist, but it was even shorter waiting time than pre covid.
And I have regular access to my GP and dsn.
And if you have another very low hypo, ring for an ambulance and get assessed by the hospital doctors who are wise to hypoglycaemia happening in T1s.

It is your health and only you can do this, only you are in charge of your health.

jonathan183 said:

I made reference to Dr Bernstein's book as I thought it might help provide an avenue for investigation ... I consider him an expert - I am not. I'll go with the explanation provided by a type 1 diabetic for over 65 years and a doctor who treats diabetics.

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While Bernstein is definitely an expert, and has done lots to change diabetes care for the better, this doesn't mean everything he's written should be taken as gospel without questioning and investigating.
Mind, I'm not saying he's wrong, I simply don't know enough about the subject to even have an opinion about it, but knowledge and insight changes over time, and differs between experts of equal education and experience.
In my opinion it's always worth questioning where a particular bit of information comes from, what studies were done to reach a conclusion etc., even if it is information supplied by an expert.

Antje77 said:

While Bernstein is definitely an expert, and has done lots to change diabetes care for the better, this doesn't mean everything he's written should be taken as gospel without questioning and investigating.
Mind, I'm not saying he's wrong, I simply don't know enough about the subject to even have an opinion about it, but knowledge and insight changes over time, and differs between experts of equal education and experience.
In my opinion it's always worth questioning where a particular bit of information comes from, what studies were done to reach a conclusion etc., even if it is information supplied by an expert.

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According to his bibliography, he has published 4 books on diabetes care.
https://www.wikidoc.org/index.php/Richard_K._Bernstein. The most recent publication date is 2007. Now most of the papers that discuss crystalised insulin or insulin granules in the beta cells are from 2015 onwards, so there remains a question as to whether Bernstein is clairvoyant or a soothsayer. I do not see any revised editions or updated releases. Just saying......

As wikipedia says - awaiting validation? Or have I got the wrong Bernstein? (I've previous on that)

BUT I note that he is a Fellow of the American College of Endocrinology so may have been given advance information. His wikipedia listing is currently under dispute and has warnings of potential bias. Seems he has been quiet since 2011.

When I read granules in that link it made me think of Acetylcholine stored in vesicles at the ends of cholinergic neurons. when a nerve impulse arrives at the terminal of a motor neuron , acetylcholine is released into the neuromuscular junction .the vesicles are like granules but not crystalline in nature.

jonathan183 said:

Have re-read Bernstein uses the term granules ... I incorrectly introduced the term crystal

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As some recently published studies are now showing, there may be crystals involved in the granules. However, the science is new, and the evidence seems thin. Thank you for correcting that post, the term granules is established for being observed in beta cells. It may have been a prescient remark you made but it may be vindicated in time. We have all learnt something from that.

JohnEGreen said:

When I read granules in that link it made me think of Acetylcholine stored in vesicles at the ends of cholinergic neurons. when a nerve impulse arrives at the terminal of a motor neuron , acetylcholine is released into the neuromuscular junction .the vesicles are like granules but not crystalline in nature.

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Just for a laugh, I found this learned paper on collagen vesicles in MUSSELS. It may not read across to human muscles, but does indicate the possibility of liquid crystalline vesicle storage.

https://pubs.acs.org/doi/full/10.1021/acs.langmuir.9b01932