In rat islets, progesterone caused a prompt concentration-dependent inhibition of glucose-stimulated insulin release with an IC50 of 10 μM at 8.4 mM glucose. The inhibition was specific since both testosterone and 17β-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 μM. 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 β-cell plasma membrane. These effects would be classified as either AI or AIIb in the Mannheim classification of nongenomically initiated steroid actions.
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Research Article|
October 01 2001
Progesterone Inhibits Insulin Secretion by a Membrane Delimited, Non-genomic Action
Susanne G. Straub;
Susanne G. Straub
1The Department of Molecular Medicine, College of Veterinary Medicine, Cornell University, Ithaca, New York
4Novartis Biomedical Research Institute, Summit, New Jersey
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Geoffrey W. G. Sharp;
Geoffrey W. G. Sharp
1The Department of Molecular Medicine, College of Veterinary Medicine, Cornell University, Ithaca, New York
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Martin D. Meglasson;
Martin D. Meglasson
2Max-Planck-Institute for Biophysical Chemistry, Department of Neurobiology, Goettingen, Germany
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Christopher J. De Souza
Christopher J. De Souza
3Pharmacia and Upjohn, Inc., Kalamazoo, Michigan, USA
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Publisher: Portland Press Ltd
Online ISSN: 1573-4935
Print ISSN: 0144-8463
© 2001 Plenum Publishing Corporation
2001
Biosci Rep (2001) 21 (5): 653–666.
Citation
Susanne G. Straub, Geoffrey W. G. Sharp, Martin D. Meglasson, Christopher J. De Souza; Progesterone Inhibits Insulin Secretion by a Membrane Delimited, Non-genomic Action. Biosci Rep 1 October 2001; 21 (5): 653–666. doi: https://doi.org/10.1023/A:1014773010350
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