Abstract
Inhibitors of 11β-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 11β-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.
| Original language | English |
|---|---|
| Pages (from-to) | 619-627 |
| Number of pages | 9 |
| Journal | Trends in Endocrinology and Metabolism |
| Volume | 21 |
| Issue number | 10 |
| DOIs | |
| Publication status | Published - Oct 2010 |
Keywords
- 11-beta-Hydroxysteroid Dehydrogenase Type 1
- Aminopyridines
- Animals
- Diabetes Mellitus, Type 2
- Hydrocortisone
- Hypoglycemic Agents
- Hypothalamo-Hypophyseal System
- Mice
- Mice, Knockout
- Mice, Transgenic
- Pituitary-Adrenal System
- Sulfonamides
