>So how does imidazole propionate work against metformin?
Next, the researchers did a long series of experiments to find the pathway of imidazole propionate, complex and full of the names of 800 strange kinases(eight hundred is an exaggeration, not so much), so here is a brief summary of this pathway.
Metformin activates AMPK, which actually promotes the phosphorylation of AMPK T172. The researchers found that the phosphorylation of T172 promoted by metformin was reduced in the presence of imidazole propionate. This effect is due to increased phosphorylation of AMPK S485.
Then who moved the S485? Looking for previous research, I found a kinase that promotes S485 phosphorylation, Akt. Exactly, the experimental data also showed that Imidazole propionate can promote the phosphorylation of Akt.
Okay, continue. So who makes Akt phosphorylate? The researchers first predicted a batch of target objects using the PhosphoNET database, and then eliminated them one by one, and finally found the direct target of imidazole propionate, p38γ.
Now let’s follow the logic, imidazole propionate activates p38γ, p38γ activates Akt, Akt promotes AMPK S485 phosphorylation, and AMPK S485 phosphorylation inhibits AMPK T172 phosphorylation, which is the effect of metformin.
Really, it’s complicated.
In fact, researchers have previously discovered that another pathway of imidazole propionate is also achieved through p38γ, but in the end this pathway is implemented in insulin receptor substrate 1(IRS1) directly affects insulin sensitivity.