Beta-cell growth brake
DYRK1A kinase↓
Also searched as DYRK1A kinase.
You want it eased, not ripped off: the same brake operates in many tissues, and releasing it everywhere is not a good idea.
In depth
A kinase that holds adult human beta cells out of the cell cycle. Release it and human beta cells start dividing again — which is why it is the single most studied target in beta-cell regeneration.
What drives it
Neuronal overexcitation increases it.
Excitotoxic calcium turns DYRK1A up. Verbatim: 'Intraneuronal calcium is increased due to excitotoxicity... and activates calpain I, which proteolyzes Dyrk1A and in turn activates it' (J Biol Chem 2015, doi 10.1074/jbc.M115.645507, PMC4463463). this is a rise in DYRK1A kinase activity by cleavage; full-length protein falls in the same process. doi 10.1074/jbc.M115.645507 · PMC4463463
What it drives
It reduces Beta-cell renewal.
The brake, with a genetic counterfactual. Verbatim: 'we find that analogs of the small molecule harmine function as a new class of human beta cell mitogenic compounds. We also define dual-specificity tyrosine-regulated kinase-1a (DYRK1A) as the likely target' (PMID 25751815). The counterfactual: 'silencing DYRK1A in human beta cells fully reproduces the harmine-induced proliferation' - the genetic knockdown reproduces the drug, so the target is confirmed, not inferred. Nothing on this blend inhibits DYRK1A. This edge exists to explain why beta-cell regeneration is hard, not to license a claim. PMID 25751815
It reduces Protects insulin cells.
DYRK1A is expressed in pancreatic beta-cells, where it phosphorylates NFAT and restrains the proliferation program. PMID 25751815
Blends that modulate it
Each blend page names this pathway and carries the study behind its claim.
See it on the map
Open the causal map to follow this pathway upstream and downstream, arrow by arrow, each with its study.