ArticleDiabetes2009
11beta-hydroxysteroid dehydrogenase type 1 regulates glucocorticoid-induced insulin resistance in skeletal muscle.
Article in Diabetes, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers, 2 of them syntheses that pooled it.
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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.
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Who cites it
65 citing papers in PubMed, 2 syntheses or guidelines pooled it, 164 citations in OpenAlex.
- Prevalence and prognostic value of preexisting sarcopenia in patients with mechanical ventilation: a systematic review and meta-analysis.Critical care (London, England) · 2022Pooled it
- Diagnosis, prevalence, and mortality of sarcopenia in dialysis patients: a systematic review and meta-analysis.Journal of cachexia, sarcopenia and muscle · 2022Pooled it
- Cryptotaenia japonica extract attenuates glucocorticoid-induced muscle atrophy via regulation of the AKT/mTOR-FOXO/E3 ubiquitin ligase axis.Frontiers in physiology · 2026Article
- Sarcopenia is associated with mortality among newly initiated peritoneal dialysis patients with end-stage kidney disease: a longitudinal follow-up study.BMC nephrology · 2025Article
- Glucocorticoid-Mediated Skeletal Muscle Atrophy: Molecular Mechanisms and Potential Therapeutic Targets.International journal of molecular sciences · 2025Review
- ATP-binding cassette family C member 1 constrains metabolic responses to high-fat diet in male mice.The Journal of endocrinology · 2024Article
- A Prospective Cohort Study Evaluating Impact of Sarcopenia on Hospitalization in Patients on Continuous Ambulatory Peritoneal Dialysis.Scientific reports · 2024Article
- Size matters: the biochemical logic of ligand type in endocrine crosstalk.Life metabolism · 2024Article
- Article
- Hepatic-Specific FGF21 Knockout Abrogates Ovariectomy-Induced Obesity by Reversing Corticosterone Production.International journal of molecular sciences · 2023Article
- Effect of Omega-3 Rich High-Fat Diet on Markers of Tissue Lipid Metabolism in Glucocorticoid-Treated Mice.International journal of molecular sciences · 2023Article
- Glucocorticoid activation of anti-inflammatory macrophages protects against insulin resistance.Nature communications · 2023Article
- Circadian Clock Desynchronization and Insulin Resistance.International journal of environmental research and public health · 2022Review
- 11β-HSD1 contributes to age-related metabolic decline in male mice.The Journal of endocrinology · 2022Article
- Inhibition of 11β-hydroxysteroid dehydrogenase 1 relieves fibrosis through depolarizing of hepatic stellate cell in NASH.Cell death & disease · 2022Article
- Keeping It Local in Metabolic Disease: Adipose Tissue Paracrine Signaling and Insulin Resistance.Diabetes · 2022Review
- Multi-Targeted Molecular Docking, Pharmacokinetics, and Drug-Likeness Evaluation of Okra-Derived Ligand Abscisic Acid Targeting Signaling Proteins Involved in the Development of Diabetes.Molecules (Basel, Switzerland) · 2021Article
- Glucose Metabolism in Burns-What Happens?International journal of molecular sciences · 2021Review
- Lifestyle interventions for the prevention and treatment of hypertension.Nature reviews. Cardiology · 2021Review
- Molecular Mechanisms of Glucocorticoid-Induced Insulin Resistance.International journal of molecular sciences · 2021Review
5 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 3 institutions in 1 country.
Funding
Abstract
objectiveGlucocorticoid excess is characterized by increased adiposity, skeletal myopathy, and insulin resistance, but the precise molecular mechanisms are unknown. Within skeletal muscle, 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) converts cortisone (11-dehydrocorticosterone in rodents) to active cortisol (corticosterone in rodents). We aimed to determine the mechanisms underpinning glucocorticoid-induced insulin resistance in skeletal muscle and indentify how 11beta-HSD1 inhibitors improve insulin sensitivity. RESEARCH DESIGN AND
methodsRodent and human cell cultures, whole-tissue explants, and animal models were used to determine the impact of glucocorticoids and selective 11beta-HSD1 inhibition upon insulin signaling and action.
resultsDexamethasone decreased insulin-stimulated glucose uptake, decreased IRS1 mRNA and protein expression, and increased inactivating pSer(307) insulin receptor substrate (IRS)-1. 11beta-HSD1 activity and expression were observed in human and rodent myotubes and muscle explants. Activity was predominantly oxo-reductase, generating active glucocorticoid. A1 (selective 11beta-HSD1 inhibitor) abolished enzyme activity and blocked the increase in pSer(307) IRS1 and reduction in total IRS1 protein after treatment with 11DHC but not corticosterone. In C57Bl6/J mice, the selective 11beta-HSD1 inhibitor, A2, decreased fasting blood glucose levels and improved insulin sensitivity. In KK mice treated with A2, skeletal muscle pSer(307) IRS1 decreased and pThr(308) Akt/PKB increased. In addition, A2 decreased both lipogenic and lipolytic gene expression.
conclusionsPrereceptor facilitation of glucocorticoid action via 11beta-HSD1 increases pSer(307) IRS1 and may be crucial in mediating insulin resistance in skeletal muscle. Selective 11beta-HSD1 inhibition decreases pSer(307) IRS1, increases pThr(308) Akt/PKB, and decreases lipogenic and lipolytic gene expression that may represent an important mechanism underpinning their insulin-sensitizing action.
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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.