Hello all. I ran across this article referencing some research in Pennsylvania it’s from 2 years ago and there is no update that I could find. They said in the article that the will be doing canine and human trials.
This is exciting for several reasons.
No need for refrigeration
No injections
It’s faster onset
Lowers hypo risk
Cheaper to make
It is a transfected lettuce plant but unlike current insulin where bacteria is transfected with insulin, this lettuce is transfected with pro insulin so that sounds like it will also have c peptide
This sounds like a very promising study
Does anyone else have any info on it.? Anything more current than 2023.
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That’s interesting, I’ll be looking forward to seeing human trials. This might be an effective way for an oral insulin. Curious as to dosage.
I just knew salad was good for you! 
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Quoting from the article:
Recent clinical studies show that injection via insulin pens can cause insulin to reach the bloodstream so quickly that hypoglycemia, or blood sugar levels that dip below the healthy range, may result.
That’s an AI summary. The graphic immediately above the quote references “oral versus injectable insulin”; i.e. the graphic is referencing Afrezza. It also includes the difficult to read reference to “Healthy - Natural Insulies” (the graphic is low resolution).
The reference is to a paper published by a dentist:
Although clinical insulin has been in use for several decades, it is missing one of the three peptides that occur in natural insulin.
And from there everything goes downhill.
Whatever.
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Penn Today seems to me like a legitimate publication of the University of Pennsylvania’s communication department. Maybe the person writing the article doesn’t really understand the science involved and maybe the editing is subpar. It’s not a scientific journal, more a promotional publication, but I don’t get your belief that Afreeza is involved or that it’s AI generated. Seems like interesting basic research to me by an interesting researcher.
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Sounds very interesting!!! I hope the process works, it’d be great!
I actually found the original study. It’s kind of dry and difficult to follow. I agree someone found that and created the article for the university newspaper. I was looking for the original but I found at least a better more detailed report of that Affordable oral proinsulin bioencapsulated in plant cells regulates blood sugar levels similar to natural insulin - ScienceDirect
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This paper has some red flags, but since I’m not in the drug development business I don’t know if they add up to be a problem. I found the paper interesting in a maybe in 20 years kind of way. Since y’all kept discussing it I dug a little deeper.
First, we know insulin delivered orally doesn’t work without something to help it survive the digestive system. This paper from 2024 has a good summary of the reasons why insulin doesn’t survive in Section 2. While looking for a good explainer I found lots of papers saying “we found an oral insulin that works in mice”. Apparently it is a low bar to get over these days.
Second, the lead author was claiming a lettuce based gene therapy cured diabetic mice 20 years ago. Not even remotely possible. This doesn’t mean the lettuce insulin working in mice didn’t happen. But. I am no longer thinking this might be a possibility in 20 years.
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Thanks to @Timothy for posting the link to that paper. I was wondering how proinsulin going directly into the bloodstream was cleaved into insulin/c-peptide as that normally happens in the Beta cells.
The following snip takes that into consideration. Evidently there is no problem with proinsulin being cleaved other than in the Beta cells.
The proinsulin gene (Pris) present at the downstream of the cholera toxin-B (CTB) subunit in the construct was modified (Fig. S2) from the native human proinsulin gene by replacing the native protein cleavagesite at the junction of subunit b/c and c/a by furin cleavage sites (RRKR). The ubiquitous presence of furin protease in all human cell types [52] eliminates dependency of proinsulin maturation only in pancreatic cells. Other modifications include presence of [hinge region](Hinge Region - an overview | ScienceDirect Topics) (GPGP) and additional furin cleavage site between CTB and Pris to facilitate proper folding and excision of Pris after CTB mediated internalization into gut epithelium cells, respectively (Fig. S2). A total of three furin cleavage sites are present in the modified proinsulin protein, so designated as Fx3Pris. The similarity of the transcriptional and translational machinery of bacteria and chloroplast facilitates evaluation of the expression cassette in bacteria before proceeding with chloroplast transformation. Detection of ∼22.5 and ∼45 kDa protein in all tested clones but not in untransformed cells in western blots probed with anti-CTB antibody confirmed expression of the CTB-Proinsulin fusion protein as monomer and dimer, respectively (Fig. S1E).
It was interesting to me that the insulin enters the bloodstream by way of the liver (what the article calls “the gut-liver axis”). I seem to remember that those who had the MiniMed implanted pump also received insulin mediated by the liver and they reported that they had few lows. No idea what the mechanism there is that prevents lows but the implantable pump has seemed to me like an unfortunate lost opportunity. This oral proinsulin would obviously be on the opposite end of invasiveness but perhaps with a benefit in common.
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I don’t think that’s what is says; they modified the cleavages of proinsulin so that they were attacked by a generic protease, the “furin protease” in your quote. Proinsulin requires a proinsulin-specific protease. Proinsulin is released from the pancreas at a somewhat lower rate than insulin, presumably because of the rapid proinsulin-specific cleavage in the pancreas.
Proinsulin is also active in the same way as insulin - it enables glucose transport into the cells - but proinsulin has a longer half life in the blood stream.
However I think the point here is that a proinsulin which still has its cleavage can be efficiently cleaved in other cells. It’s not clear to me how efficiently proinsulin could be transported into cells, cleaved, then, as an insulin, transported out of them…
It’s also not clear to me why; why bother? Since proinsulin has at least some ability to enable at least some glucose transport why not just use that?
It’s important to remember that glucose transport is crucial to all eukaryotes and that insulin (with those famous disulphide bonds) seems to occur consistent. Here in invertebrates:
Here in unicellular eukaryotes:
That sort-of traces back a billion years; sort of because working out that kind of thing from a billion year old fossil is impossible. Yet plants (well, the “higher” plants) only date back half a billion years; they evolved much more recently than “animals”, which is why “animal” is used for anything older than plants.
This leads to the question of whether algae, because of their evolutionary association with plants, currently produce insulin:
I found the use of the word “antigen” in that paper slightly confusing. They obtained two human-insulin specific antibodies. The “antigen” for these is human insulin. They then used these against the various extracts to detect things that the antibody reacted to.
A careful read of the “Discussion” at the end of that paper is well worth while.
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