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Comparative effects of efaroxan and beta-carbolines on the secretory activity of rodent and human beta cells

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UNSPECIFIED (2003) Comparative effects of efaroxan and beta-carbolines on the secretory activity of rodent and human beta cells. In: 4th International Symposium on Agmatine and Imidazoline Systems, San Diego, CA, APR 09-11, 2003. Published in: AGMATINE AND IMIDAZOLINES: THEIR NOVEL RECEPTORS AND ENZYMES, 1009 pp. 167-174. ISBN 1-57331-498-6. ISSN 0077-8923. doi:10.1196/annals.1304.019

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Official URL: http://dx.doi.org/10.1196/annals.1304.019

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Abstract

The pancreatic beta-cell expresses an imidazoline-binding site that is involved in the regulation of insulin secretion. This site is pharmacologically atypical in comparison with the I-1 and I-2 sites described in other tissues, and it has been classified as I-3. The structural requirements for binding of ligands to the I-3 site have not been fully defined, although a range of synthetic I-3 ligands have been characterized in functional terms. Evidence has been presented that an endogenous I-3 ligand may exist, because extracts of brain contain an active principle that stimulates insulin secretion in a manner consistent with the involvement of I-3 sites. The active component has not been identified but has been equated with the long-sought clonidine displacing substance (CDS) that is proposed as the endogenous ligand for imidazoline-binding sites. Recent evidence has indicated that one active component of CDS may be a beta-carboline, but it is not known whether beta-carbolines can stimulate insulin secretion. Thus, we have studied the effects of beta-carbolines on insulin secretion and cytosolic Ca2+ levels in rodent and human islet cells. The results reveal that harmane, pinoline, and norharmane cause a dose- and glucose-dependent increase in insulin secretion but show that this response differs in a number of ways from that elicited by the well-characterized I-3-agonist, efaroxan. Thus, beta-carbolines represent a new class of insulin secretagogues, although it remains unclear whether their action is mediated solely by I-3 sites in the beta cell.

Item Type: Conference Item (UNSPECIFIED)
Subjects: Q Science
Series Name: ANNALS OF THE NEW YORK ACADEMY OF SCIENCES
Journal or Publication Title: AGMATINE AND IMIDAZOLINES: THEIR NOVEL RECEPTORS AND ENZYMES
Publisher: NEW YORK ACAD SCIENCES
ISBN: 1-57331-498-6
ISSN: 0077-8923
Editor: Piletz, JE and Regunathan, S and Ernsberger, P
Official Date: 2003
Dates:
DateEvent
2003UNSPECIFIED
Volume: 1009
Number of Pages: 8
Page Range: pp. 167-174
DOI: 10.1196/annals.1304.019
Publication Status: Published
Title of Event: 4th International Symposium on Agmatine and Imidazoline Systems
Location of Event: San Diego, CA
Date(s) of Event: APR 09-11, 2003

Data sourced from Thomson Reuters' Web of Knowledge

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