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ID: 16510.0, MPI für biophysikalische Chemie / Neurobiologie (Prof. Reinhard Jahn)
Progesterone inhibits insulin secretion by a membrane delimited, non-genomic action
Authors:Straub, S. G.; Sharp, G. W. G.; Meglasson, M. D.; De Souza, C. J.
Language:English
Date of Publication (YYYY-MM-DD):2001-10
Title of Journal:Bioscience Reports
Volume:21
Issue / Number:5
Start Page:653
End Page:666
Review Status:Peer-review
Audience:Not Specified
Abstract / Description:In rat islets, progesterone caused a prompt concentration- dependent inhibition of glucose-stimulated insulin release with an IC50 of 10 muM at 8.4 mM glucose. The inhibition was specific since both testosterone and 17beta-estradiol had no such effect. The degree of inhibition was similar in islets from male and female rats. The inhibition was not blocked in PTX-treated islets thus ruling out the Gi/Go proteins as mediators of the inhibition. Progesterone inhibited both glucose- and BayK-8644-stimulated insulin Secretion in HIT-T15 cells and the IC50 vs. 10 mM glucose was also 10 muM. There was no effect on intracellular cyclic AMP concentration in the presence 0.2 and 10 mM glucose. Progesterone decreased [Ca2+](i) under all conditions tested. The decrease in [Ca2+](i), was due to blockade of the L-type voltage-dependent Ca2+, channels. Under Ca2+-free conditions, progesterone did not inhibit the stimulation of insulin release due to the combination of glucose, phorbol ester and Forskolin. Thus blockade of Ca2+ entry appears to be the sole mechanism by which progesterone inhibits insulin release. As progesterone covalently linked to albumin had a similar inhibitory effect as progesterone itself, it is concluded that the steroid acts at the outer surface of the beta-cell plasma membrane. These effects would be classified as either AI or AIIb in the Mannheim classification of nongenomically initiated steroid actions.
Free Keywords:insulin secretion; pancreatic beta-cell; steroids; membrane effects
Comment of the Author/Creator:Date: 2001, OCT
External Publication Status:published
Document Type:Article
Communicated by:N. N.
Affiliations:MPI für biophysikalische Chemie/Abt. Reinhard Jahn / 190
External Affiliations:Cornell Univ, Coll Vet Med, Dept Mol Med, Ithaca, NY 14853 USA; Pharmacia & Upjohn Inc, Kalamazoo, MI 49007 USA; Novartis Biomed Res Inst, Summit, NJ 07901 USA
Identifiers:URL:http://springerlink.metapress.com/content/6qtv771k...
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