Will treating diabetes with 11β-HSD1 inhibitors affect the HPA axis?

被引：28
|
作者：
Harno, Erika
White, Anne [1 ]
机构：
[1] Univ Manchester, Acad Hlth Sci Ctr, Fac Life Sci, Manchester M13 9PL, Lancs, England
来源：
TRENDS IN ENDOCRINOLOGY AND METABOLISM | 2010年 / 21卷 / 10期
关键词：
11-BETA-HYDROXYSTEROID DEHYDROGENASE TYPE-1; SPLANCHNIC CORTISOL PRODUCTION; PITUITARY-ADRENAL AXIS; DIET-INDUCED OBESITY; METABOLIC SYNDROME; ADIPOSE-TISSUE; VISCERAL OBESITY; MICE; LIVER; MELLITUS;
D O I：
10.1016/j.tem.2010.06.004
中图分类号：
R5 [内科学];
学科分类号：
1002 ; 100201 ;
摘要：
Inhibitors of 11 beta-HSD1 are in clinical trials for the treatment of type 2 diabetes. These compounds act by decreasing the cortisol generated in liver and adipose tissue, and therefore reducing tissue-specific gluconeogenesis and fatty acid metabolism. However, there is concern that reduction in tissue-regenerated cortisol might decrease feedback to the hypothalamic-pituitary-adrenal (HPA) axis, resulting in upregulation of cortisol from the adrenal gland. This review considers evidence from 11 beta-HSD1 knockout and transgenic mice, inhibitor studies and results from clinical trials evaluating HPA axis biomarkers. It is clear that analysis of the HPA axis is not sufficiently detailed, and there is a need to understand the subtle changes in the axis associated with pulsatility, diurnal rhythm and stress.
引用
收藏
页码：619 / 627
页数：9
相关论文
共 50 条
  • [21] Discovery and biological evaluation of adamantyl amide 11β-HSD1 inhibitors
    Webster, Scott P.
    Ward, Peter
    Binnie, Margaret
    Craigie, Eilidh
    McConnell, Kirsty M. M.
    Sooy, Karen
    Vinter, Andy
    Seckl, Jonathan R.
    Walker, Brian R.
    BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2007, 17 (10) : 2838 - 2843
  • [22] Functional Effects of Polymorphisms in the Human Gene Encoding 11β-Hydroxysteroid Dehydrogenase Type 1 (11β-HSD1): A Sequence Variant at the Translation Start of 11β-HSD1 Alters Enzyme Levels
    Malavasi, Elise L. V.
    Kelly, Val
    Nath, Nikita
    Gambineri, Alessandra
    Dakin, Rachel S.
    Pagotto, Uberto
    Pasquali, Renato
    Walker, Brian R.
    Chapman, Karen E.
    ENDOCRINOLOGY, 2010, 151 (01) : 195 - 202
  • [23] Population Pharmacokinetic/Pharmacodynamic Model of Subcutaneous Adipose 11β-Hydroxysteroid Dehydrogenase Type 1 (11β-HSD1) Activity After Oral Administration of AMG 221, a Selective 11β-HSD1 Inhibitor
    Gibbs, John P.
    Emery, Maurice G.
    McCaffery, Ian
    Smith, Brian
    Gibbs, Megan A.
    Akrami, Anna
    Rossi, John
    Paweletz, Katherine
    Gastonguay, Marc R.
    Bautista, Edgar
    Wang, Minghan
    Perfetti, Riccardo
    Daniels, Oranee
    JOURNAL OF CLINICAL PHARMACOLOGY, 2011, 51 (06) : 830 - 841
  • [24] 11-Beta-hydroxysteroid dehydrogenase type 1 (11β-HSD1) inhibitors in Type 2 diabetes mellitus and obesity
    Hughes, Katherine A.
    Webster, Scott P.
    Walker, Brian R.
    EXPERT OPINION ON INVESTIGATIONAL DRUGS, 2008, 17 (04) : 481 - 496
  • [25] The Expression of Omental 11β-HSD1 Is Not Increased in Severely Obese Women with Metabolic Syndrome
    Michalaki, Marina
    Kyriazopoulou, Venetsana
    Antonacopoulou, Anna
    Koika, Vasiliki
    Nikolaou, Marinos
    Tsoukas, Athanasios
    Kalfarentzos, Fotis
    Vagenakis, Apostolos G.
    Voukelatou, Georgia
    Papavassiliou, Athanasios G.
    OBESITY FACTS, 2012, 5 (01) : 104 - 111
  • [26] Safety, efficacy and weight effect of two 11β-HSD1 inhibitors in metformin-treated patients with type 2 diabetes
    Heise, T.
    Morrow, L.
    Hompesch, M.
    Haering, H. -U.
    Kapitza, C.
    Abt, M.
    Ramsauer, M.
    Magnone, M. -C.
    Fuerst-Recktenwald, S.
    DIABETES OBESITY & METABOLISM, 2014, 16 (11) : 1070 - 1077
  • [27] Optimization of novel di-substituted cyclohexylbenzamide derivatives as potent 11β-HSD1 inhibitors
    McMinn, Dustin L.
    Rew, Yosup
    Sudom, Athena
    Caille, Seb
    DeGraffenreid, Michael
    He, Xiao
    Hungate, Randall
    Jiang, Ben
    Jaen, Juan
    Julian, Lisa D.
    Kaizerman, Jacob
    Novak, Perry
    Sun, Daqing
    Tu, Hua
    Ursu, Stefania
    Walker, Nigel P. C.
    Yan, Xuelei
    Ye, Qiuping
    Wang, Zhulun
    Powers, Jay P.
    BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2009, 19 (05) : 1446 - 1450
  • [28] Discovery of potent and selective inhibitors of 11β-HSD1 for the treatment of metabolic syndrome
    Richards, Steven
    Sorensen, Bryan
    Jae, Hwan-Soo
    Winn, Marty
    Chen, Yixian
    Wang, Jiahong
    Fung, Steven
    Monzon, Katina
    Frevert, Ernst U.
    Jacobson, Peer
    Sham, Hing
    Link, J. T.
    BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2006, 16 (24) : 6241 - 6245
  • [29] Synthesis and biological evaluation of heterocycle containing adamantane 11β-HSD1 inhibitors
    Yeh, Vince S. C.
    Patel, Jyoti R.
    Yong, Hong
    Kurukulasuriya, Ravi
    Fung, Steven
    Monzon, Katina
    Chiou, William
    Wang, Jiahong
    Stolarik, Deanne
    Imade, Hovis
    Beno, David
    Brune, Michael
    Jacobson, Peer
    Sham, Hing
    Link, J. T.
    BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2006, 16 (20) : 5414 - 5419
  • [30] Antidiabetic effects of 11β-HSD1 inhibition in a mouse model of combined diabetes, dyslipidaemia and atherosclerosis
    Lloyd, D. J.
    Helmering, J.
    Cordover, D.
    Bowsman, M.
    Chen, M.
    Hale, C.
    Fordstrom, P.
    Zhou, M.
    Wang, M.
    Kaufman, S. A.
    Veniant, M. M.
    DIABETES OBESITY & METABOLISM, 2009, 11 (07) : 688 - 699
12345