Looks like this might be BIG.
Over the past few years, there have been about 5 compounds that are all DYRK1A inhibitors (supportive of the case) that induce beta cell replication in HUMAN beta cells. These 5 compounds come from 3 independent research groups. Getting beta cells to grow in mice is super easy. Humans ... not so easy.
That's important because it's not artificially stimulating the same beta cells to produce more, stop them from dying, or reduce insulin resistance, urinating it out, or stop a liver from producing glucose. No, it's inducing them to undergo mitosis, and several proteins related to proliferation limitation and senescence like p16 and p57 are reduced.
As you may know, human beta cells replicate during an early-age-window of something like birth to 5-10 years old. After that, it's SEVERELY limited by various forms of replication inhibition. Probably by p16 and p57 or similar. There are reports of accelerated telomere shortening, but these multiple studies call that into question. The vast majority of donor cells would be from older patients. They ALL proliferated. Taking cycloastragenol might not be a horrible idea, but telomeres may not be the problem.
My guess is that in large animals with long life expectancies, this is a limiting system to prevent hypoglycemia and/or cancer. According to http://www.ncbi.nlm....les/PMC3904605/, p57 is involved. This is not entirely surprising. The cells we get typically take us to 20-30, which ensures species survival. But we're living longer now. Mice don't live so long. The beta cells are not protected to the same level.
This is important, and possibly huge, actually. Even if it's not used in humans, it would also be applicable to accelerate beta cell growth from lab-grown cells: http://diabetes.diab...6/1496.full.pdf
The compounds are:
- Harmine (well known natural DYRK1A inhibitor that is also an MAOI — http://www.ncbi.nlm....es/PMC4690535/)
- INDY (a lab-created compound — http://www.ncbi.nlm....es/PMC4690535/)
- GNF4877 (lab-created aminopyrazine compound — http://www.ncbi.nlm....es/PMC4639830/)
- GNF7156 (lab-created aminopyrazine compound — http://www.ncbi.nlm....es/PMC4639830/)
- 5-IT / 5-iodotubercidin (annotated adenosine kinase inhibitor — http://www.ncbi.nlm....ubmed/26953159)
It's important that all of these are also DYRK1A inhibitors, even if that's one of the off-target effects for what a compound was initially created or discovered for. 5-IT is an "annotated adenosine kinase inhibitor," but:
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Edited by Logjam, 21 July 2016 - 10:59 PM.