Identifies Epac2 as a necessary intracellular target for sulfonylurea-induced insulin release, alongside K(ATP) channels.
Epac2 targeting should not alter sulfonylurea use; leaves open its role in human insulin secretion pending validation studies.
Sulfonylurea drugs are used in type 2 diabetes mellitus therapy to induce release of endogenous insulin from pancreatic beta cells. They act on sulfonylurea receptors, which are the regulatory subunits of adenosine triphosphate (ATP)-sensitive potassium ion (K(ATP)) channels and cause channel closure to trigger exocytosis. Epac2 was identified as an intracellular target for sulfonylurea drugs, providing a potential nonelectrogenic signaling component to the mechanism of action for these agents. Commonly used sulfonylureas such as tolbutamide and glibenclamide induced Epac2 activation with distinct kinetic profiles. Epac2(-/-) mice failed to respond to sulfonylureas, suggesting that both sulfonylurea receptors and Epac2 are necessary for the action of these drugs. These data require that the cellular and physiological effects of drugs that alter the open state of the K(ATP) channel be reassessed.
No takes yet. Share an insight, caveat, or question.
Simon A. Hinke (2009) studied this question.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: