11β-Hydroxysteroid dehydrogenase inhibition improves cognitive function in healthy elderly men and type 2 diabetics
| Autor: | June Noble, Alasdair M.J. MacLullich, Ian J. Deary, Brian R. Walker, Joyce L.W. Yau, Thekkepat C. Sandeep, Jonathan R. Seckl |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
medicine.medical_specialty
Multidisciplinary medicine.diagnostic_test business.industry Carbenoxolone Hippocampus Type 2 diabetes Biological Sciences medicine.disease Crossover study Endocrinology Addison Disease Internal medicine 11-beta-Hydroxysteroid Dehydrogenase Type 1 medicine Humans Cortisone Cognitive decline Lipid profile business Cushing Syndrome Glucocorticoids hormones hormone substitutes and hormone antagonists Glucocorticoid medicine.drug |
| Zdroj: | Proceedings of the National Academy of Sciences. 101:6734-6739 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.0306996101 |
| Popis: | In aging humans and rodents, inter-individual differences in cognitive function have been ascribed to variations in long-term glucocorticoid exposure. 11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) regenerates the active glucocorticoid cortisol from circulating inert cortisone, thus amplifying intracellular glucocorticoid levels in some tissues. We show that 11β-HSD1, but not 11β-HSD2, mRNA is expressed in the human hippocampus, frontal cortex, and cerebellum. In two randomized, double-blind, placebo-controlled crossover studies, administration of the 11β-HSD inhibitor carbenoxolone (100 mg three times per day) improved verbal fluency ( P < 0.01) after 4 weeks in 10 healthy elderly men (aged 55-75 y) and improved verbal memory ( P < 0.01) after 6 weeks in 12 patients with type 2 diabetes (52-70 y). Although carbenoxolone has been reported to enhance hepatic insulin sensitivity in short-term studies, there were no changes in glycemic control or serum lipid profile, nor was plasma cortisol altered. 11β-HSD1 inhibition may be a new approach to prevent/ameliorate cognitive decline. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|