#1

I would like to shine some light on this topic. As we age, our pancreatic beta cells, the cells that make insulin, decrease. We produce an agent (called DRK1a) that gradually reduces the replication rate of the beta cells. For some of us that process is too aggressive and consequently insulin levels are too low. This isn’t T1DB, but it is kind of similar because the lack of insufficient insulin causes glucose to increase in the blood instead of getting into the cells.

I am pretty sure that is what is happening with me: low fasting insulin (1-3), increasingly high fasting glucose, tested negative for LADA. Low insulin is also associated with Alzheimers. I am low BMI, low BP, low pulse – all also risks for Alzheimers, plus family history.

Metformin can address the high glucose. But what about the pancreas?

Dr. Andrew Stewart at Mt Sinai has done a presentation on a new therapy now in trials. His lab (Peng Wang, PhD) did a massive screen of molecules and found one that does increase Beta Cell replication in human cells, and has been found to be harmless in amounts far exceeding what is required to stimulate the BCell replication. The molecule is called Harmine. A version of this (it is plant based) has been used by native societies in combination with other substances to create the hallucinogenic Ayauesca. The Stewart lab at Mt. Sinai found that Harmine works by disenabling DRK1A, effectively taking off the brakes so that B cells can replicate.

The presentation describes all this and shows a bottle of 100mg capsules of Harmine that is being used in trials. A phase one trial has been completed.

I would so appreciate it if anyone has more information about Harmine, has actually taken it, or ideas of how to procure it. To my knowledge It is not outside the lab in pill form. But someone fabricated these capsules for Mt. Sinai to use in the trials. Are there places you can go to have lab-powders fabricated for you into pills?

Highly recommend the youtube: Human Pancreatic Beta Cell Regeneration.

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#2

I think you mean this video

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#3

Mine is 2.5 mcU/mL which is considered lower end normal. I was told that lower fasting insulin levels can indicate good insulin sensitivity, which is beneficial for metabolic health. I don’t have any negatives in connection with this reading unless I’m missing something or not paying attention to some signs.

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#4

Thanks RapAdmin. It’s about time I learned to post a link.

Lara – If my glucose were normal, I would consider that my low insulin indicated good sensitivity, as you said yours does. But since my glucose is high it leads me to think there is insufficient insulin to get the glucose admitted to the cells, so it just hangs out in the blood. But may-be I am wrong-- maybe the cells are getting enough glucose but the liver is just making too damn much. I hope the endocrinologist I will be seeing can sort this out.

#5

How high is your fasting glucose? Mine is in the 90s range and I would like it to be lower but it doesn’t go lower no matter what I try.

#6

Mine was 114 this morning. A bit higher than usual because I had to take a break from the metformin. But it is usually about 100. Too high. Last Ha1C was 5.9.

#7

FWIW

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#8

This says that Harmine has psychoactive effects, whereas the Andrew Smith work says that Harmine itself is not psychoactive, but is usually combined with other substances that are psychoactive to make the compound Ayahuasca.

Have you used Harmine? Can you share any information about it from your experience?

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#9

Hi @Deborah_Hall dis you ever figure out your (too?) low insulin? Did it normalize after you stopped the PCSK9i?

#10

I would guess part of this relates to the non renewal of Beta cells which is a standard part of aging. Also it appears that senescent cells actually are capable of being adipocytes. Hence if stem cells are becoming senescent in the pancreas it explains why people have a fat threshold.

#11

Hi Neo, I did not have the insulin retested – it was tested twice and both times was borderline low, like 3. C peptide also low. I do not know whether the PCSK9i had any role to play in any of this but now I suspect not. My fasting blood glucose has been high, like 90-100 for many years. I did get LADA ruled out – but now I suspect I have a simmering Type 1 that is starting to progress. Have been testing morning fasting BG which ranges from a low of about 105 on days that I fast over 16 hours, swim laps for an hour and then test, to about 120-138 on mornings when I test after fasting 13 hours but before exercising. I am on 2000 metformin and also 1200 Berberine plus all the supps – cinnamon, gymnema sylvestre, benfotiamine, and plenty of others. In the meantime, while I wait for the appointment with the diabetes specialist (which has gotten pushed back twice), I have started taking a very small dose of Harmine HCl. I ordered Rybelsus which should be here very soon. I am now pretty certain that this is T1DM, as I have heredity and family history.

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#12

Have you ever tried to test your BG after just 8-10 h fast? Mine is in low 90s after 8 h fast, however if I wait 13-15 h to test it’s always above 100. If I exercise during fast and then measure, it’ll be in a range of 110.

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#13

Thanks - my insulin and C peptide also have been low, but when I tried a PCK9i holiday it did not change anything

I did have a slight increase in HbA1c, so will wear a CGM for a bit and see what that looks like for a while before going back to taking repatha.

What is involved in testing and ruling that out?

#14

LADA testing: blood test that measures Glutamic Acid Decarboxylase, and Islet Cell Antibodies. You don’t get to see a value --it comes back as negative or positive. Mine came back negative. About 15% of type 1 DM do not show positive for the antibodies – that might happen if it is early in the disease progression. Or, it might be Type 2. But the low C-peptide and low insulin strongly suggest to me that it is Type 1, especially with the genetics and that I am quite thin, fit, etc.

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#15

Thanks – that is interesting. I need to start testing under a range of conditions to try to figure this out. I think I read that there is “brittle” DM, where the glucose readings can be all over the place with no apparent logic.

#16

@Deborah_Hall Have you tried wearing one of the latest gen CGMs (continuous glucose monitors) for two weeks or so?

#17

No, should do that. Which one do you recommend?

#18

A few years ago it felt like Dexcom was best, but with the Abbott’s Freestyle Libre 3 the gap between that and Dexcom 7 is quite small.

The main thing is that Dexcom ban be calibrated against finger pricks, while Libre 3 is slightly smaller and last a few extra days.

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#19

What are the common factors of and the differences between CR/ fasting and Rapamycin? Why are CR/ fasting beneficial for the pancreas, but rapamycin might damage it? Do we have to fast or follow a fasting mimicking diet with extremely low carbs after a rapamycin dose? Is a high blood glucose the cause of the pancreas damage under rapamycin? Does the body work like a state machine with clearly defined states, and the combination of ‘no protein/calories available’ signaled by Rapamycin won’t mix with eating a lot of protein or sugar at the same time?

#20

Deborah, I’m curious. Can you see a measurable result when on Metformin or not? If you have good insulin sensitivity, it is likely that Metformin will do little to nothing for you. I found for my condition that I got zero result from Metformin.