ReviewDiabetologia2014
Tissue-specific dysregulation of cortisol regeneration by 11βHSD1 in obesity: has it promised too much?
Review in Diabetologia, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
21 citing papers in PubMed, 53 citations in OpenAlex.
- Safety, tolerability, pharmacodynamics and pharmacokinetics following once-daily doses of BI 187004, an inhibitor of 11 beta-hydroxysteroid dehydrogenase-1, over 28 days in patients with type 2 diabetes mellitus and overweight or obesity.Diabetes, obesity & metabolism · 2023Trial
- Selective Inhibition of 11beta-Hydroxysteroiddehydrogenase-1 with BI 187004 in Patients with Type 2 Diabetes and Overweight or Obesity: Safety, Pharmacokinetics, and Pharmacodynamics After Multiple Dosing Over 14 Days.Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association · 2022Trial
- Inhibition of 11β-Hydroxysteroid dehydrogenase-1 with AZD4017 in patients with nonalcoholic steatohepatitis or nonalcoholic fatty liver disease: A randomized, double-blind, placebo-controlled, phase II study.Diabetes, obesity & metabolism · 2022Trial
- Diet-induced weight loss alters hepatic glucocorticoid metabolism in type 2 diabetes mellitus.European journal of endocrinology · 2020Trial
- Glucocorticoid Excess Increases Hepatic 11β-HSD-1 Activity in Humans: Implications in Steroid-Induced Diabetes.The Journal of clinical endocrinology and metabolism · 2015Trial
- DSOK-0011 Potentially Regulates Circadian Misalignment and Affects Gut Microbiota Composition in Activity-Based Anorexia Model.The International journal of eating disorders · 2026Article
- Current Understanding of the Pathophysiology of Idiopathic Intracranial Hypertension.Current neurology and neuroscience reports · 2025Review
- Glucocorticoids and HPA axis regulation in the stress-obesity connection: A comprehensive overview of biological, physiological and behavioural dimensions.Clinical obesity · 2025Review
- The Role of microRNA in the Regulation of Cortisol Metabolism in the Adipose Tissue in the Course of Obesity.International journal of molecular sciences · 2024Article
- Age-related increase in the expression of 11β-hydroxysteroid dehydrogenase type 1 in the hippocampus of male rhesus macaques.Frontiers in aging neuroscience · 2024Article
- Zebrafish: A New Promise to Study the Impact of Metabolic Disorders on the Brain.International journal of molecular sciences · 2022Review
- Vertical sleeve gastrectomy normalizes circulating glucocorticoid levels and lowers glucocorticoid action tissue-selectively in mice.Frontiers in endocrinology · 2022Article
- Safety, tolerability, pharmacokinetics and pharmacodynamics of single oral doses of BI 187004, an inhibitor of 11beta-hydroxysteroid dehydrogenase-1, in healthy male volunteers with overweight or obesity.Clinical diabetes and endocrinology · 2021Article
- Novel 2-(Adamantan-1-ylamino)Thiazol-4(5International journal of molecular sciences · 2021Article
- Exploring the Temporal Relation between Body Mass Index and Corticosteroid Metabolite Excretion in Childhood.Nutrients · 2020Article
- Glucocorticoid Metabolism in Obesity and Following Weight Loss.Frontiers in endocrinology · 2020Review
- Copeptin and insulin resistance: effect modification by age and 11 β-HSD2 activity in a population-based study.Journal of endocrinological investigation · 2018Article
- Drug-induced obesity and its metabolic consequences: a review with a focus on mechanisms and possible therapeutic options.Journal of endocrinological investigation · 2017Review
- Aldosterone and the Mineralocorticoid Receptor: Risk Factors for Cardiometabolic Disorders.Current hypertension reports · 2015Review
- Cortisol dysregulation in obesity-related metabolic disorders.Current opinion in endocrinology, diabetes, and obesity · 2015Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
Abstract
Cushing's syndrome, caused by increased production of cortisol, leads to metabolic dysfunction including visceral adiposity, hypertension, hyperlipidaemia and type 2 diabetes. The similarities with the metabolic syndrome are striking and major efforts have been made to find obesity-associated changes in the regulation of glucocorticoid action and synthesis, both at a systemic level and tissue level. Obesity is associated with tissue-specific alterations in glucocorticoid metabolism, with increased activity of the glucocorticoid-regenerating enzyme 11β-hydroxysteroid dehydrogenase type 1 (11βHSD1) in subcutaneous adipose tissue and decreased conversion of cortisone to cortisol, interpreted as decreased 11βHSD1 activity, in the liver. In addition, genetic manipulation of 11βHSD1 activity in rodents can either induce (by overexpression of Hsd11b1, the gene encoding 11βHSD1) or prevent (by knocking out Hsd11b1) obesity and metabolic dysfunction. Taken together with earlier evidence that non-selective inhibitors of 11βHSD1 enhance insulin sensitivity, these results led to the hypothesis that inhibition of 11βHSD1 might be a promising target for treatment of the metabolic syndrome. Several selective 11βHSD1 inhibitors have now been developed and shown to improve metabolic dysfunction in patients with type 2 diabetes, but the small magnitude of the glucose-lowering effect has precluded their further commercial development.This review focuses on the role of 11βHSD1 as a tissue-specific regulator of cortisol exposure in obesity and type 2 diabetes in humans. We consider the potential of inhibition of 11βHSD1 as a therapeutic strategy that might address multiple complications in patients with type 2 diabetes, and provide our thoughts on future directions in this field.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.