AJP - Endocrinology and Metabolism, Vol 256, Issue 1 E19-E24, Copyright © 1989 by American Physiological Society
Interleukin 1 is a potent stimulator of islet insulin secretion and phosphoinositide hydrolysis
W. S. Zawalich and K. C. Zawalich
Yale University School of Nursing, New Haven, Connecticut 06536-0740.
The insulin stimulatory effect of 7 mM glucose on isolated perifused rat
islets is dramatically potentiated by the monokine interleukin 1 (IL-1). At
levels (10(-10) -10(-8) M) noted in vivo during sepsis, it reversibly
amplifies peak second phase insulin release to the hexose. At 2.75 mM
glucose, however, IL-1 has no effect on insulin secretion. IL-1 also
potentiates glyceraldehyde (2 mM)- and alpha-ketoisocaproate (5 mM)-induced
insulin secretion. In islets whose phosphoinositides were prelabeled with
myo-[2-3H]inositol, 2.0-5.0 nM IL-1 increases the efflux of [3H]inositol
from subsequently perifused islets, the parallel accumulation of labeled
inositol phosphates, and insulin secretion in the simultaneous presence of
7 mM glucose but not 2.75 mM glucose. In support of these in vitro
observations, the in vivo infusion of IL-1 (40 micrograms/kg body wt)
elevated circulating plasma insulin levels two-to fourfold. These results
establish IL-1 as a potent, readily reversible, glucose-dependent modulator
of stimulated insulin secretion and further suggest that its positive
impact on insulin release is mediated, at least in part, by
phosphoinositide-derived second messenger molecules. IL-1-induced insulin
secretion may participate in the multiple metabolic and immunologic
adaptations occurring during sepsis.
