Diabetes
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Ullrich, S.
Right arrow Articles by Lang, F.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ullrich, S.
Right arrow Articles by Lang, F.
Social Bookmarking
Add to CiteULike   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

Diabetes 54:1090-1099, 2005
© 2005 by the American Diabetes Association, Inc.

Serum- and Glucocorticoid-Inducible Kinase 1 (SGK1) Mediates Glucocorticoid-Induced Inhibition of Insulin Secretion

Susanne Ullrich1, Susanne Berchtold1, Felicia Ranta1, Guiscard Seebohm1, Guido Henke1, Adrian Lupescu1, Andreas F. Mack2, Cho-Ming Chao3, Jiping Su3, Roland Nitschke4, Dorothea Alexander5, Björn Friedrich6, Peer Wulff7, Dietmar Kuhl8, and Florian Lang1

1 Department for Physiology, University of Tübingen, Tübingen, Germany
2 Deparment of Anatomy, University of Tübingen, Tübingen, Germany
3 Department for Neurophysiology, University of Cologne, Cologne, Germany
4 Institut für Biologie I, Life Imaging Facility, Freiburg, Germany
5 Department of Orthopedics, University of Tübingen, Tübingen, Germany
6 Department of Internal Medicine, University of Tübingen, Tübingen, Germany
7 Department of Clinical Neurobiology, University Hospital of Neurology, Heidelberg, Germany
8 Department of Biology, Chemistry, and Pharmacy, Free University Berlin, Berlin, Germany

Glucocorticoid excess predisposes to the development of diabetes, at least in part through impairment of insulin secretion. The underlying mechanism has remained elusive. We show here that dexamethasone upregulates transcription and expression of the serum- and glucocorticoid-inducible kinase 1 (SGK1) in insulin-secreting cells, an effect reversed by mifepristone (RU486), an antagonist of the nuclear glucocorticoid receptor. When coexpressed in Xenopus oocytes, SGK1 increases the activity of voltage-gated K+ channel Kv1.5. In INS-1 cells, dexamethasone stimulates the transcription of Kv1.5, increases the repolarizing outward current, reduces peak values of [Ca2+]i oscillations, and decreases glucose-induced insulin release. The latter effect is reversed by K+ channel blockers 4-aminopyridine and tetraethylammonium and by a more selective Kv1.5 channel inhibitor MSD-D. Dexamethasone also increases expression of Kv1.5 in mouse islets and reduces glucose-induced insulin secretion, an effect reversed by MSD-D. In islets isolated from wild-type but not SGK1 knockout mice, dexamethasone significantly blunted glucose-, forskolin-, and phorbol myristic acid-induced insulin release. In conclusion, dexamethasone stimulates the transcription of SGK1, which in turn upregulates the activity of voltage-gated K+ channels. Increased K+ channel activity reduces Ca2+ entry through voltage-gated Ca2+ channels and insulin release.

Address correspondence and reprint requests to Dr. Susanne Ullrich, Institut für Physiologie Gmelinstrasse, 5 D-72076 Tübingen, Germany. E-mail: susanne.ullrich{at}uni-tuebingen.de


Add to CiteULike CiteULike   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:


Home page
 J Mol EndocrinolHome page
H. Ghanaat-Pour, Z. Huang, M. Lehtihet, and A. Sjoholm
Global expression profiling of glucose-regulated genes in pancreatic islets of spontaneously diabetic Goto-Kakizaki rats
J. Mol. Endocrinol., August 1, 2007; 39(2): 135 - 150.
[Abstract] [Full Text] [PDF]

Home page
 Circ. Res.Home page
G. Seebohm, N. Strutz-Seebohm, R. Birkin, G. Dell, C. Bucci, M. R. Spinosa, R. Baltaev, A. F. Mack, G. Korniychuk, A. Choudhury, et al.
Regulation of Endocytic Recycling of KCNQ1/KCNE1 Potassium Channels
Circ. Res., March 16, 2007; 100(5): 686 - 692.
[Abstract] [Full Text] [PDF]

Home page
 Physiol. Rev.Home page
F. Lang, C. Bohmer, M. Palmada, G. Seebohm, N. Strutz-Seebohm, and V. Vallon
(Patho)physiological Significance of the Serum- and Glucocorticoid-Inducible Kinase Isoforms.
Physiol Rev, October 1, 2006; 86(4): 1151 - 1178.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
K. M. Boini, A. M. Hennige, D. Y. Huang, B. Friedrich, M. Palmada, C. Boehmer, F. Grahammer, F. Artunc, S. Ullrich, D. Avram, et al.
Serum- and glucocorticoid-inducible kinase 1 mediates salt sensitivity of glucose tolerance.
Diabetes, July 1, 2006; 55(7): 2059 - 2066.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
F. Ranta, D. Avram, S. Berchtold, M. Dufer, G. Drews, F. Lang, and S. Ullrich
Dexamethasone induces cell death in insulin-secreting cells, an effect reversed by exendin-4.
Diabetes, May 1, 2006; 55(5): 1380 - 1390.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
H. Oberkofler, K. Klein, T. K. Felder, F. Krempler, and W. Patsch
Role of Peroxisome Proliferator-Activated Receptor-{gamma} Coactivator-1{alpha} in the Transcriptional Regulation of the Human Uncoupling Protein 2 Gene in INS-1E Cells
Endocrinology, February 1, 2006; 147(2): 966 - 976.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Diabetes Diabetes Care Clinical Diabetes Diabetes Spectrum
Copyright © 2005 by the American Diabetes Association.