Interaction of β-Cell Activity and IL-1 Concentration and Exposure Time in Isolated Rat Islets of Langerhans

  1. Jørn Nerup
  1. Steno Memorial Hospital and the Hagedom Research Laboratory Gentofte, Denmark
  1. Address correspondence and reprint requests to Dr. Jørn Nerup, Steno Memorial Hospital, 2 Niels Steensens Vej, 2820 Gentofte, Denmark


This study was designed to test the hypothesis that target-cell activity influences the degree and time course of interleukin 1β (IL-1β)–mediated β-cellimpairment 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-1β. β-Cell activity was modulated by glucose and nonglucose agents (15 mM L-leucine and 10 μM of long-acting somatostatin analogue SMS 201–995). In 11 mM glucose, 2000 ng/L of IL-1β caused inhibition of insulin release after ∼6 h of exposure to IL-1β; in 3.3 mM glucose culture, onset of inhibition was delayed by this IL-1β concentration until after 48 h of exposure. Similarly, stimulation and suppression of β-cell function with L-leucine and SMS 201–995, respectively, resulted in acceleration and delay of IL-1β-mediated inhibition. The dose-response curve of the IL-1β effect was shifted left- and rightward during high and low β-cell activity, respectively. In analogy, increasing IL-1β concentration, exposure time, and β-cell activity resulted in increasing islet disintegration. Thus, the resting β-cell is more resistant to IL-1β-mediated impairment than the working β-cell.

  • Received November 3, 1988.
  • Revision received May 16, 1989.
  • Accepted May 16, 1989.
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