Manipulation of Transmembrane Transport by Synthetic K Ionophore Depsipeptides and Its Implications in Glucose‐Stimulated Insulin Secretion in β‐Cells.

García‐Calvo, José; Torroba, Tomás; Brañas‐Fresnillo, Virginia; Perdomo, Germán; Cózar‐Castellano, Irene; Li, Yu‐Hao; Legrand, Yves‐Marie; Barboiu, Mihail

The cyclic depsipeptide cereulide toxin it is a very well‐known potassium electrogenic ionophore particularly sensitive to pancreatic beta cells. The mechanistic details of its specific activity are unknown. Here, we describe a series of synthetic substituted cereulide potassium ionophores that cause impressive selective activation of glucose‐induced insulin secretion in a constitutive manner in rat insulinoma INS1E cells. Our study demonstrates that the different electroneutral K transport mechanism exhibited by the anionic mutant depsipeptides when compared with classical electrogenic cereulides can have an important impact of pharmacological value on glucose‐stimulated insulin secretion.

DEPSIPEPTIDES; PANCREATIC beta cells; INSULIN; SECRETION; IONOPHORES

Chemistry - A European Journal, 2019, Vol 25, Issue 39, p9287

0947-6539

Academic Journal

10.1002/chem.201901372