An in vivo microdialysis coupled with liquid chromatography/tandem mass spectrometry study of cortisol metabolism in monkey adipose tissue

摘要: Abstract It is postulated that elevated tissue concentrations of cortisol may be associated with the development metabolic syndrome, obesity, and type 2 diabetes. The 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) enzyme regenerates from inactive cortisone in tissues such as liver adipose. To better understand pivotal role 11β-HSD1 disease development, an vivo microdialysis assay coupled liquid chromatography/tandem mass spectrometry (LC/MS/MS) analysis using stable isotope-labeled (SIL) a substrate was developed. This overcomes limitations existing methodologies suffer radioactivity exposure analytical sensitivity specificity concerns. Analyte extraction efficiencies ( E d ) were evaluated by retrodialysis. conversion SIL-cortisone to SIL-cortisol rhesus monkey adipose studied. Solutions containing 100, 500, 1000 ng/mL locally delivered through implanted 30-mm probe tissue. At delivery rate 1.0 0.5 μL/min, values for between 58.7 ± 5.6% n  = 4) 72.7 ± 1.3%  = 4), whereas at 0.3 μL/min reached nearly 100%. presence activities demonstrated production during infusion. methodology could applied metabolism studies other mammalian species.