Insulinotropic action of AICA riboside. II. Secretory, metabolic and cationic aspects

Preincubation of rat pancreatic islets with AICA riboside (0.1 to 1.0mM) caused a concentration-related stimulation of both 45Ca net uptake and insulin release evoked by 8.3 mM D-glucose, but failed to affect the conversion of D-[5-3H]glucose to 3HOH, the generation of 14CO2 and 14C-labelled amino acids or acidic metabolites from D-[U-14C]glucose, and the islet content in ATP, ADP or AMP. The secretory response to AICA riboside was not suppressed in islets preincubated with methotrexate. AICA riboside caused a progressive decrease in 86Rb outflow from prelabelled islets perifused at 2.8 or 6.0mM D-glucose. This effect faded out at a higher concentration of D-glucose (16.7 mM), in which case AICA riboside nevertheless provoked a delayed, progressive and not rapidly reversible enhancement of insulin output. At concentrations up to 0.4 mM, ZTP only exerted a modest effect on the activity of KATP-channels in inside-out patches of dispersed mouse islet cells. These findings raise the question whether the insulinotropic action of AICA riboside may be attributable to the sequential generation of ZMP, ZDP and ZTP from the nucleoside.