HIV protease inhibitors: suppression of insulin secretion by inhibition of voltage-dependent K+ currents and anion currents.

We have shown before that the human immunodeficiency virus (HIV) protease inhibitors ritonavir and nelfinavir, but not indinavir, suppress insulin secretion from mouse pancreatic B-cells via reduction of the cytosolic free calcium concentration ([Ca(2+)](c)). This was not because of an effect on ATP-dependent K(+) channels (K(ATP) channels) or L-type Ca(2+) channels. The study was intended to elucidate the mechanisms by which distinct HIV protease inhibitors decrease [Ca(2+)](c) and thus evoke their adverse side effect on insulin release.