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-cell is
species dependent
Yale University School of Nursing, New Haven, Connecticut 06536-0740
The capacity of 20 mM glucose to desensitize insulin release was determined. A prior
exposure to 20 mM glucose impaired the response of rat islets to
subsequent restimulation. Compared with control islets, insulin
secretory rates measured 25-30 min after the onset of 20 mM
glucose stimulation were reduced by 75%. Restimulation of
glucose-desensitized islets with 20 mM glucose plus 500 nM forskolin
resulted in a dramatic enhancement of both phases of secretion. In
contrast to the desensitization of rat islets induced by prior 20 mM
glucose exposure, mouse islets were immune to this adverse effect of
the hexose. Prior exposure to 20 mM glucose had no adverse effect on
glucose usage rates. The activation of phospholipase C in
glucose-desensitized rat islets was compromised when compared with
control islets. The impairment could not be accounted for by a decrease
in immunoreactive content of several major phospholipase C isozymes
(
1 or
1) or their partitioning between the membrane and cytosolic
compartments. In contrast to rat islets, prior exposure of mouse islets
to 20 mM glucose for 180 min had no effect on inositol phosphate
accumulation. These observations document an additional difference
between rat and mouse islets and suggest that the evolution of
desensitization is a consequence of the impaired activation of
phospholipase C in rat islets.
phospholipase C; inositol phosphates; toxicity; islets
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