The α 2-adrenergic agonist clonidine concentration-dependently depresses glucose-stimulated insulin secretion from INS-1 cells. Static insulin secretion was performed with cells subjected to stepwise elevation of glucose concentration from 3 to 11 mM for 30 min in the absence or presence of clonidine and determined by a standard insulin radioimmunoassay. Cells exposed to 11 mM glucose (closed circle at the far left) released significantly more insulin than those to 3 mM glucose (open circle) (, ). In the concentration range of 0.003–10 μM, clonidine produced a concentration-dependent inhibition of insulin release induced by 11 mM glucose. The inhibition became statistically significant at 0.01 μM clonidine (, ) and was statistically significant at higher clonidine concentrations (, ). The subthreshold and ED50 concentration of clonidine were calculated to be 0.003 and 4 μM, respectively. In this and all other figures, data are presented as means ± SEM. Statistical significance was evaluated by one-way ANOVA, followed by least significant difference (LSD) test. and versus 11 mM glucose-treated group.
