Sub-chronic administration of the 11β-HSD1 inhibitor, carbenoxolone, improves glucose tolerance and insulin sensitivity in mice with diet-induced obesity
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Ashley Taylor
Abstract
We have examined the metabolic effects of daily administration of carbenoxolone (CBX), a naturally occurring 11β-hydroxysteroid dehydrogenase (11β-HSD1) inhibitor, in mice with high fat diet-induced insulin resistance and obesity. Eight-week-old male Swiss TO mice placed on a synthetic high fat diet received daily intraperitoneal injections of either saline vehicle or CBX over a 16-day period. Daily administration of CBX had no effect on food intake, but significantly lowered body weight (1.1- to 1.2-fold) compared to saline-treated controls. Non-fasting plasma glucose levels were significantly decreased (1.6-fold) by CBX treatment on day 4 and remained lower throughout the treatment period. Circulating plasma corticosterone levels were not significantly altered by CBX treatment. Plasma glucose concentrations of CBX-treated mice were significantly reduced (1.4-fold) following an intraperitoneal glucose load compared with saline controls. Similarly, after 16-day treatment with CBX, exogenous insulin evoked a significantly greater reduction in glucose concentrations (1.4- to 1.8-fold). 11β-HSD1 gene expression was significantly down-regulated in liver, whereas glucocorticoid receptor gene expression was increased in both liver and adipose tissue following CBX treatment. The reduced body weight and improved metabolic control in mice with high fat diet-induced obesity upon daily CBX administration highlights the potential value of selective 11β-HSD1 inhibition as a new route for the treatment of type 2 diabetes and obesity.
©2008 by Walter de Gruyter Berlin New York
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Artikel in diesem Heft
- Highlight: 59th Mosbach Kolloquium
- The role of long non-coding RNAs in chromatin structure and gene regulation: variations on a theme
- The histone H1 family: specific members, specific functions?
- ATP-dependent chromatosome remodeling
- Role of histone modifications in defining chromatin structure and function
- Differential loss of histone H3 isoforms mono-, di- and tri-methylated at lysine 4 during X-inactivation in female embryonic stem cells
- Disentanglement of protease substrate repertoires
- p53-dependent repression of the human MCL-1 gene encoding an anti-apoptotic member of the BCL-2 family: the role of Sp1 and of basic transcription factor binding sites in the MCL-1 promoter
- 5′-End maturation of tRNA in Aquifex aeolicus
- Smurf1 directly targets hPEM-2, a GEF for Cdc42, via a novel combination of protein interaction modules in the ubiquitin-proteasome pathway
- Purification and characterization of natural Ara h 8, the Bet v 1 homologous allergen from peanut, provides a novel isoform
- Human butyrylcholinesterase components differ in aryl acylamidase activity
- Ribosome display and selection of human anti-CD22 scFvs derived from an acute lymphocytic leukemia patient
- Sub-chronic administration of the 11β-HSD1 inhibitor, carbenoxolone, improves glucose tolerance and insulin sensitivity in mice with diet-induced obesity
- Inhibitory effect of the sugarcane cystatin CaneCPI-4 on cathepsins B and L and human breast cancer cell invasion
