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PMID: 15071189 Published · ppublish English Clinical Trial Comparative Study Journal Article Randomized Controlled Trial Research Support, Non-U.S. Gov't

11Beta-hydroxysteroid dehydrogenase inhibition improves cognitive function in healthy elderly men and type 2 diabetics.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 101 ·No. 17 ·2004-04-27 ·Pages 6734-9

Sandeep TC, Yau JL, MacLullich AM, Noble J, Deary IJ, Walker BR, Seckl JR

Abstract

In aging humans and rodents, inter-individual differences in cognitive function have been ascribed to variations in long-term glucocorticoid exposure. 11beta-Hydroxysteroid dehydrogenase type 1 (11beta-HSD1) regenerates the active glucocorticoid cortisol from circulating inert cortisone, thus amplifying intracellular glucocorticoid levels in some tissues. We show that 11beta-HSD1, but not 11beta-HSD2, mRNA is expressed in the human hippocampus, frontal cortex, and cerebellum. In two randomized, double-blind, placebo-controlled crossover studies, administration of the 11beta-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. 11beta-HSD1 inhibition may be a new approach to prevent/ameliorate cognitive decline.

MeSH Terms
11-beta-Hydroxysteroid Dehydrogenases/antagonists & inhibitors,genetics,metabolism Aged Case-Control Studies Cognition Cross-Over Studies Diabetes Mellitus, Type 2/enzymology,physiopathology Female Humans Male Middle Aged Placebos RNA, Messenger/genetics
Chemicals
Placebos RNA, Messenger 11-beta-Hydroxysteroid Dehydrogenases
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Sandeep Thekkepat C
Endocrinology Unit, School of Molecular and Clinical Medicine, University of Edinburgh, Molecular Medicine Centre, Western General Hospital, Edinburgh EH4 2XU, United Kingdom.
Yau Joyce L W
MacLullich Alasdair M J
Noble June
Deary Ian J
Walker Brian R
Seckl Jonathan R
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.0306996101
Published
2004-04-27
Epub
2004-00-07
Pages
6734-9
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC404114
Subset
IM
Grants
Wellcome Trust · United Kingdom
Corrections
CommentIn
PMID: 15096596
External Links
PubMed source DOI: 10.1073/pnas.0306996101 PMC Full Text View journal details
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