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
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
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