Interaction of beta-cell activity and IL-1 concentration and exposure time in isolated rat islets of Langerhans

Abstract

This study was designed to test the hypothesis that target-cell activity influences the degree and time course of interleukin 1 beta (IL-1 beta)-mediated beta-cell impairment in vitro. Functional and morphological studies were performed in cultured newborn rat islets of Langerhans exposed from 6 h to 6 days to 50-2000 ng/L recombinant human IL-1 beta. Beta-Cell activity was modulated by glucose and nonglucose agents (15 mM L-leucine and 10 microM of long-acting somatostatin analogue SMS 201-995). In 11 mM glucose, 2000 ng/L of IL-1 beta caused inhibition of insulin release after approximately 6 h of exposure to IL-1 beta; in 3.3 mM glucose culture, onset of inhibition was delayed by this IL-1 beta concentration until after 48 h of exposure. Similarly, stimulation and suppression of beta-cell function with L-leucine and SMS 201-995, respectively, resulted in acceleration and delay of IL-1 beta-mediated inhibition. The dose-response curve of the IL-1 beta effect was shifted left- and rightward during high and low beta-cell activity, respectively. In analogy, increasing IL-1 beta concentration, exposure time, and beta-cell activity resulted in increasing islet disintegration. Thus, the resting beta-cell is more resistant to IL-1 beta-mediated impairment than the working beta-cell.