K-ATP channel openers protect rat islets against the toxic effect of streptozotocin

We examined the influence of two K-ATP channel openers, diazoxide and an an alog (NNC 55-0118), on experimental beta-cell damage induced by streptozoto cin (STZ; 0.5 mmol/l), Rat pancreatic islets were exposed to diazoxide or N NC 55-0118 for 30 min and were further incubated for 30 min after the addit ion of STZ. The islets were then washed and cultured for 24 h, Islets expos ed to STZ alone showed extensive morphological damage, reduced glucose;oxid ation, low insulin content, and severely impaired glucose-stimulated insuli n secretion and proinsulin biosynthesis. Islets treated with STZ in the pre sence of the channel openers (0.03-0.30 mmol/l) showed dose-dependent prese rvation of the morphology and improved glucose oxidation rates, insulin con tent, and secretion. NNC 55-0118 was capable of fully counteracting the STZ impairment, whereas diazoxide Pled a less protective effect. NNC 55-0118 d id not counteract STZ-induced depression of islet NAD levels when examined 2 h after STZ exposure, which suggests that the mechanism of action by NNC 55-0118 is not; through an inhibition of poly(ADP-ribose) polymerase, The r esults illustrate that K-ATP channel openers can protect insulin-producing cells against toxic damage, an effect that may be of use in subjects with o ngoing insulitis.