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Hormone Molecular Biology and Clinical Investigation

Editor-in-Chief: Chetrite, Gérard S.

Editorial Board: Alexis, Michael N. / Baniahmad, Aria / Beato, Miguel / Bouillon, Roger / Brodie, Angela / Carruba, Giuseppe / Chen, Shiuan / Cidlowski, John A. / Clarke, Robert / Coelingh Bennink, Herjan J.T. / Darbre, Philippa D. / Drouin, Jacques / Dufau, Maria L. / Edwards, Dean P. / Falany, Charles N. / Fernandez-Perez, Leandro / Ferroud, Clotilde / Feve, Bruno / Flores-Morales, Amilcar / Foster, Michelle T. / Garcia-Segura, Luis M. / Gastaldelli, Amalia / Gee, Julia M.W. / Genazzani, Andrea R. / Greene, Geoffrey L. / Groner, Bernd / Hampl, Richard / Hilakivi-Clarke, Leena / Hubalek, Michael / Iwase, Hirotaka / Jordan, V. Craig / Klocker, Helmut / Kloet, Ronald / Labrie, Fernand / Mendelson, Carole R. / Mück, Alfred O. / Nicola, Alejandro F. / O'Malley, Bert W. / Raynaud, Jean-Pierre / Ruan, Xiangyan / Russo, Jose / Saad, Farid / Sanchez, Edwin R. / Schally, Andrew V. / Schillaci, Roxana / Schindler, Adolf E. / Söderqvist, Gunnar / Speirs, Valerie / Stanczyk, Frank Z. / Starka, Luboslav / Sutter, Thomas R. / Tresguerres, Jesús A. / Wahli, Walter / Wildt, Ludwig / Yang, Kaiping / Yu, Qi


CiteScore 2017: 2.48

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Source Normalized Impact per Paper (SNIP) 2017: 0.830

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Volume 15, Issue 2

Issues

The role and regulation of 11β-hydroxysteroid dehydrogenase type 1 in obesity and the metabolic syndrome

Roland H. Stimson
  • Corresponding author
  • Centre for Cardiovascular Science, Queen’s Medical Research Institute, 47 Little France Crescent, Edinburgh, EH16 4TJ, UK
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Brian R. Walker
Published Online: 2013-06-11 | DOI: https://doi.org/10.1515/hmbci-2013-0015

Abstract

The cortisol regenerating enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) amplifies tissue glucocorticoid levels, particularly in the liver and adipose tissue. The importance of this enzyme in causing metabolic disease was highlighted by transgenic mice which over- or under-expressed 11β-HSD1; consequently, selective 11β-HSD1 inhibitors have been widely developed as novel agents to treat obesity and type 2 diabetes mellitus (T2DM). This review focuses on the importance of 11β-HSD1 in humans which has been more difficult to ascertain. The recent development of a deuterated cortisol tracer has allowed us to quantify in vivo cortisol production by 11β-HSD1. These results have been surprising, as cortisol production rates by 11β-HSD1 are at least equivalent to that of the adrenal glands. The vast majority of this production is by the liver (>90%) with a smaller contribution from subcutaneous adipose tissue and possibly skeletal muscle, but with no detectable production from visceral adipose tissue. This tracer has also allowed us to quantify the tissue-specific regulation of 11β-HSD1 observed in obesity and obesity-associated T2DM, determine the likely basis for this dysregulation, and identify obese patients with T2DM as the group most likely to benefit from selective inhibition of 11β-HSD1. Some of these inhibitors have now reached Phase II clinical development, demonstrating efficacy in the treatment of T2DM. We review these results and discuss whether selective 11β-HSD1 inhibitors are likely to be an important new therapy for metabolic disease.

Keywords: cortisol; diabetes; 11β-hydroxysteroid dehydrogenase type 1; obesity; tracer methodology

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About the article

Corresponding author: Roland H. Stimson, Centre for Cardiovascular Science, Queen’s Medical Research Institute, 47 Little France Crescent, Edinburgh, EH16 4TJ, UK, Phone: +44-131-2426748, Fax: +44-131-2426779


Received: 2013-04-25

Accepted: 2013-05-21

Published Online: 2013-06-11

Published in Print: 2013-09-01


Citation Information: Hormone Molecular Biology and Clinical Investigation, Volume 15, Issue 2, Pages 37–48, ISSN (Online) 1868-1891, ISSN (Print) 1868-1883, DOI: https://doi.org/10.1515/hmbci-2013-0015.

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Endocrine, 2017, Volume 57, Number 1, Page 60
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Thamara C. Peixoto, Egberto G. Moura, Elaine de Oliveira, Patrícia N. Soares, Deysla S. Guarda, Dayse N. Bernardino, Xu Xue Ai, Vanessa da S. T. Rodrigues, Gabriela Rodrigues de Souza, Antonio Jorge Ribeiro da Silva, Mariana S. Figueiredo, Alex C. Manhães, and Patrícia C. Lisboa
European Journal of Nutrition, 2017
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Erwin Lemche, Oleg S. Chaban, and Alexandra V. Lemche
Frontiers in Neuroscience, 2016, Volume 10

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