Biological evaluation of diabetes-related kinases and their inhibition

Diabetes together with its related diseases represents a threat to global health. Its prevalence continues to increase year by year, and it is estimated to reach 700 million cases by 2045. Currently, the administration of exogenous insulin to control blood glucose levels remains the main therapy available because an effective and lasting cure has not yet been found. New strategies, on the other hand, aim to promote β-cell differentiation and proliferation, and one of the most interesting targets for doing this is DYRK1A kinase, which regulates cell cycle progression and is involved in differentiation and signal transduction. Through inhibition of this kinase, our compounds are able to promote β-cell regeneration and increase the amount of insulin available to patients. Combining these compounds with specific TGF-β inhibitors or GLP-1 agonists also provides significantly better results when compared with the gold standard compound harmine. Tests on various cell types show that the use of DYRK1A inhibitors may represent a promising approach for the treatment of type 1 and type 2 diabetes.