دورية أكاديمية
Effects of Obesity and Insulin on Tissue-Specific Recycling Between Cortisol and Cortisone in Men.
| العنوان: | Effects of Obesity and Insulin on Tissue-Specific Recycling Between Cortisol and Cortisone in Men. |
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| المؤلفون: | Anderson AJ; University/BHF Centre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, UK., Andrew R; University/BHF Centre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, UK.; Mass Spectrometry Core Laboratory, Edinburgh Clinical Research Facility, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, UK., Homer NZM; Mass Spectrometry Core Laboratory, Edinburgh Clinical Research Facility, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, UK., Hughes KA; University/BHF Centre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, UK., Boyle LD; University/BHF Centre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, UK., Nixon M; University/BHF Centre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, UK., Karpe F; Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Churchill Hospital, University of Oxford, Headington, Oxford, UK., Stimson RH; University/BHF Centre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, UK., Walker BR; University/BHF Centre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, UK.; Translational & Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK. |
| المصدر: | The Journal of clinical endocrinology and metabolism [J Clin Endocrinol Metab] 2021 Mar 08; Vol. 106 (3), pp. e1206-e1220. |
| نوع المنشور: | Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Oxford University Press Country of Publication: United States NLM ID: 0375362 Publication Model: Print Cited Medium: Internet ISSN: 1945-7197 (Electronic) Linking ISSN: 0021972X NLM ISO Abbreviation: J Clin Endocrinol Metab Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2017- : New York : Oxford University Press Original Publication: Springfield, Ill. : Charles C. Thomas |
| مواضيع طبية MeSH: | Cortisone/*metabolism , Hydrocortisone/*metabolism , Hyperinsulinism/*metabolism , Obesity/*metabolism, Adipose Tissue/metabolism ; Adult ; Aged ; Body Mass Index ; Cross-Over Studies ; Glucose/metabolism ; Humans ; Insulin/metabolism ; Liver/metabolism ; Male ; Middle Aged ; Muscle, Skeletal/metabolism ; Organ Specificity ; Thinness/metabolism ; United Kingdom |
| مستخلص: | Context: 11β-Hydroxysteroid dehydrogenase 1 (11βHSD1) reduces inert cortisone into active cortisol but also catalyzes reverse dehydrogenase activity. Drivers of cortisol/cortisone equilibrium are unclear. With obesity, 11βHSD1 transcripts are more abundant in adipose, but the consequences for oxidation vs reduction remain unknown. Objective: This work aimed to determine whether 11βHSD1 equilibrium in metabolic tissues is regulated by insulin and obesity. Methods: A 2-phase, randomized, crossover, single-blinded study in a clinical research facility was conducted of 10 lean and obese healthy men. 11β-Reductase and 11β-dehydrogenase activities were measured during infusion of 9,11,12,12-[2H]4-cortisol and 1,2-[2H]2-cortisone, respectively, on 2 occasions: once during saline infusion and once during a hyperinsulinemic-euglycemic clamp. Arterialized and venous samples were obtained across forearm skeletal muscle and abdominal subcutaneous adipose. Steroids were quantified by liquid chromatography-tandem mass spectrometry and adipose tissue transcripts by quantitative polymerase chain reaction. Results: Neither whole-body nor tissue-specific rates of production of cortisol or cortisone differed between lean and obese men, however insulin attenuated the diurnal decrease. Whole-body 11β-HSD1 reductase activity tended to be higher in obesity (~ 10%) and was further increased by insulin. Across adipose tissue, 11β-reductase activity was detected in obese individuals only and increased in the presence of insulin (18.99 ± 9.62 vs placebo 11.68 ± 3.63 pmol/100 g/minute; P < .05). Across skeletal muscle, 11β-dehydrogenase activity was reduced by insulin in lean men only (2.55 ± 0.90 vs 4.50 ± 1.42 pmol/100 g/minute, P < .05). Conclusions: Regeneration of cortisol is upregulated by insulin in adipose tissue but not skeletal muscle. In obesity, the equilibrium between 11β-reductase and 11β-dehydrogenase activities likely promotes cortisol accumulation in adipose, which may lead to adverse metabolic consequences. (© The Author(s) 2020. Published by Oxford University Press on behalf of the Endocrine Society.) |
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| معلومات مُعتمدة: | RG/17/1/32663 United Kingdom BHF_ British Heart Foundation; 107049/Z/15/Z United Kingdom WT_ Wellcome Trust; United Kingdom WT_ Wellcome Trust; SCAF/17/02 United Kingdom CSO_ Chief Scientist Office; RG/11/4/28734 United Kingdom BHF_ British Heart Foundation |
| فهرسة مساهمة: | Keywords: 11β-hydroxysteroid dehydrogenase 1; cortisol; cortisone; insulin; obesity |
| المشرفين على المادة: | 0 (Insulin) IY9XDZ35W2 (Glucose) V27W9254FZ (Cortisone) WI4X0X7BPJ (Hydrocortisone) |
| تواريخ الأحداث: | Date Created: 20201203 Date Completed: 20210922 Latest Revision: 20220323 |
| رمز التحديث: | 20240628 |
| مُعرف محوري في PubMed: | PMC7947841 |
| DOI: | 10.1210/clinem/dgaa896 |
| PMID: | 33270115 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1945-7197 |
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| DOI: | 10.1210/clinem/dgaa896 |