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Chronic inhibition of 11 β -hydroxysteroid dehydrogenase type 1 activity decreases hypertension, insulin resistance, and hypertriglyceridemia in metabolic syndrome.

Abstract
Metabolic syndrome is a constellation of risk factors including hypertension, dyslipidemia, insulin resistance, and obesity that promote the development of cardiovascular disease. Metabolic syndrome has been associated with changes in the secretion or metabolism of glucocorticoids, which have important functions in adipose, liver, kidney, and vasculature. Tissue concentrations of the active glucocorticoid cortisol are controlled by the conversion of cortisone to cortisol by 11 β -hydroxysteroid dehydrogenase type 1 (11 β -HSD1). Because of the various cardiovascular and metabolic activities of glucocorticoids, we tested the hypothesis that 11 β -HSD1 is a common mechanism in the hypertension, dyslipidemia, and insulin resistance in metabolic syndrome. In obese and lean SHR/NDmcr-cp (SHR-cp), cardiovascular, metabolic, and renal functions were measured before and during four weeks of administration of vehicle or compound 11 (10 mg/kg/d), a selective inhibitor of 11 β -HSD1. Compound 11 significantly decreased 11 β -HSD1 activity in adipose tissue and liver of SHR-cp. In obese SHR-cp, compound 11 significantly decreased mean arterial pressure, glucose intolerance, insulin resistance, hypertriglyceridemia, and plasma renin activity with no effect on heart rate, body weight gain, or microalbuminuria. These results suggest that 11 β -HSD1 activity in liver and adipose tissue is a common mediator of hypertension, hypertriglyceridemia, glucose intolerance, and insulin resistance in metabolic syndrome.
AuthorsChristine G Schnackenberg, Melissa H Costell, Daniel J Krosky, Jianqi Cui, Charlene W Wu, Victor S Hong, Mark R Harpel, Robert N Willette, Tian-Li Yue
JournalBioMed research international (Biomed Res Int) Vol. 2013 Pg. 427640 ( 2013) ISSN: 2314-6141 [Electronic] United States
PMID23586038 (Publication Type: Journal Article)
Chemical References
  • Glucocorticoids
  • Receptors, Leptin
  • 11-beta-Hydroxysteroid Dehydrogenase Type 1
Topics
  • 11-beta-Hydroxysteroid Dehydrogenase Type 1 (antagonists & inhibitors, biosynthesis)
  • Animals
  • Glucocorticoids (metabolism)
  • Humans
  • Hypertension (enzymology, metabolism, pathology)
  • Hypertriglyceridemia (enzymology, pathology)
  • Insulin Resistance (genetics)
  • Liver (enzymology, metabolism, physiopathology)
  • Metabolic Syndrome (enzymology, pathology)
  • Obesity (blood, enzymology, physiopathology)
  • Rats
  • Receptors, Leptin (genetics, metabolism)
  • Weight Gain

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