Plos Biology: a new strategy for promoting insulin secretion and targeted therapy for diabetes

Recently, scientists from the Netherlands published their latest research in the international journal Blos Biology . They use a structure-directed method to design cAMP analogs that activate Epac2 as a specific agonist of Epac2, thereby promoting beta islet cell synthesis. Secrete insulin. This study may provide a viable and effective solution for the treatment of diabetes by promoting insulin secretion.

cAMP is a small molecule in cell synthesis that activates intracellular proteins to regulate many biological processes, including olfactory, pacemaker activity, regulation of gene expression, insulin secretion, and many other processes. In the regulation of insulin secretion, cAMP can act on different stages of the signaling cascade to regulate insulin secretion in β-islet cells.

The researchers designed a cAMP analog by a structure-directed approach that specifically activates the cAMP response protein Epac2, activates the signaling cascade of the insulin secretory pathway, and has a stronger activation effect than cAMP. The researchers analyzed the complex crystal structure of Epac2 with several cAMP analogs to help explain the molecular basis by which cAMP analogs specifically act on Epac2 and have a strong activation. In addition, the researchers also demonstrated that chemically synthesized cAMP analogs promote glucose-induced insulin secretion in human islet cells.

In summary, in this study, the researchers designed and synthesized a cAMP analog by a structure-directed approach, and found that the analog specifically binds to Epac2 to activate the signaling cascade during insulin secretion and through structural biology. The method elucidates the molecular basis for the specificity and strong activation of the analog. This research is of great significance for the development of insulin-promoting drugs for the treatment of diabetes.