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

被引：33

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：

100201 [内科学];

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 57 条

[1]

The contribution of visceral adipose tissue to splanchnic cortisol production in healthy humans [J].

Andrew, R ;

Westerbacka, J ;

Wahren, J ;

Yki-Järvinen, H ;

Walker, BR .

DIABETES, 2005, 54 (05) :1364-1370

[2]

GLP-1 based therapy for type 2 diabetes [J].

Arulmozhi, DK ;

Portha, B .

EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES, 2006, 28 (1-2) :96-108

[3]

Liver Is the Site of Splanchnic Cortisol Production in Obese Nondiabetic Humans [J].

Basu, Rita ;

Basu, Ananda ;

Grudzien, Meagan ;

Jung, Paul ;

Jacobson, Peer ;

Johnson, Michael ;

Singh, Ravinder ;

Sarr, Michael ;

Rizza, Robert A. .

DIABETES, 2009, 58 (01) :39-45

[4]

Splanchnic cortisol production in dogs occurs primarily in the liver -: Evidence for substantial hepatic specific 11β hydroxysteroid dehydrogenase type 1 activity [J].

Basu, Rita ;

Edgerton, Dale S. ;

Singh, Ravinder J. ;

Cherrington, Alan ;

Rizza, Robert A. .

DIABETES, 2006, 55 (11) :3013-3019

[5]

Cushing's disease [J].

Bertagna, Xavier ;

Guignat, Laurence ;

Groussin, Lionel ;

Bertherat, Jerome .

BEST PRACTICE & RESEARCH CLINICAL ENDOCRINOLOGY & METABOLISM, 2009, 23 (05) :607-623

[6]

Depot-specific modulation of rat intraabdominal adipose tissue lipid metabolism by pharmacological inhibition of 11β-hydroxysteroid dehydrogenase type 1 [J].

Berthiaume, Magalie ;

Laplante, Mathieu ;

Festuccia, William ;

Gelinas, Yves ;

Poulin, Sebastien ;

Lalonde, Josee ;

Joanisse, Denis R. ;

Thieringer, Rolf ;

Deshaies, Yves .

ENDOCRINOLOGY, 2007, 148 (05) :2391-2397

[7]

Systematic review: Comparative effectiveness and safety of oral medications for type 2 diabetes Mellitus [J].

Bolen, Shari ;

Feldman, Leonard ;

Vassy, Jason ;

Wilson, Lisa ;

Yeh, Hsin-Chieh ;

Marinopoulos, Spyriclon ;

Wiley, Crystal ;

Selvin, Elizabeth ;

Wilson, Renee ;

Bass, Eric B. ;

Brancati, Frederick L. .

ANNALS OF INTERNAL MEDICINE, 2007, 147 (06) :386-399

[8]

Boyle CD, 2008, CURR OPIN DRUG DISC, V11, P495

[9]

11β-hydroxysteroid dehydrogenase type 1 inhibitors: a review of recent patents [J].

Boyle, Craig D. ;

Kowalski, Timothy J. .

EXPERT OPINION ON THERAPEUTIC PATENTS, 2009, 19 (06) :801-825

[10]

Hypothalamic-Pituitary-Adrenal Axis Abnormalities in Response to Deletion of 11β-HSD1 is Strain-Dependent [J].

Carter, R. N. ;

Paterson, J. M. ;

Tworowska, U. ;

Stenvers, D. J. ;

Mullins, J. J. ;

Seckl, J. R. ;

Holmes, M. C. .

JOURNAL OF NEUROENDOCRINOLOGY, 2009, 21 (11) :879-887

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