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Originally published In Press as doi:10.1074/jbc.M105008200 on July 30, 2001
J. Biol. Chem., Vol. 276, Issue 40, 37120-37123, October 5, 2001
Are 5-Hydroxytryptamine-preloaded -Cells an Appropriate
Physiologic Model System for Establishing That Insulin Stimulates
Insulin Secretion?*
Walter S.
Zawalich ,
Gregory J.
Tesz, and
Kathleen C.
Zawalich
From the Yale University School of Nursing, New Haven, Connecticut
06536-0740
The release and oxidation of
5-hydroxytryptamine from 5-hydroxytryptamine-preloaded -cells has
been used as a surrogate marker for insulin secretion. Findings made
using this methodology have been used to support the concept that
insulin stimulates its own release. In the present studies, the effects
of 5-hydroxytryptamine on stimulated insulin secretion from isolated
perifused rat islets was determined. When added together with
stimulatory glucose, 5-hydroxytryptamine (0.5 mM)
significantly reduced both phases of 8 mM glucose-induced
secretion and reduced the first phase of 15 mM
glucose-induced release by 60% without any effect on sustained insulin
release rates. Preloading of -cells with 0.5 mM
5-hydroxytryptamine for 3 h resulted in a more severe impairment of 15 mM glucose-induced secretion. First and second phase
release rates were reduced by 70 and 55%, respectively. In addition,
this pretreatment protocol also abolished 200 µM
tolbutamide-induced insulin secretion from perifused islets. These
findings confirm that 5-hydroxytryptamine is a powerful inhibitor of
stimulated insulin secretion. The responses of
5-hydroxytryptamine-preloaded -cells may not accurately reflect the
biochemical events occurring during the physiologic regulation of
insulin secretion. The suggestion that insulin stimulates its own
secretion based exclusively on amperometric measurements should be reconsidered.
*
These studies were supported by NIDDK, National Institutes
of Health Grant 41230 and by the American Diabetes Association.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence should be addressed: Yale University School
of Nursing, P. O. Box 9740, 100 Church St. South, New Haven, CT
06536-0740. Tel.: 203-785-5522; Fax: 203-785-6455; E-mail: walter.zawalich@yale.edu.
Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.

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Copyright © 2001 by the American Society for Biochemistry and Molecular Biology.
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