ArticleProceedings of the National Academy of Sciences of the United States of America2014
Elevated hepatic 11β-hydroxysteroid dehydrogenase type 1 induces insulin resistance in uremia.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
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Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it, 35 citations in OpenAlex.
- The link between hyperuricemia and diabetes: insights from a quantitative analysis of scientific literature.Frontiers in endocrinology · 2024Pooled it
- Altered systemic bioenergetic reserve in chronic kidney disease predisposes hearts to worse functional outcomes.Scientific reports · 2025Article
- Computational QSAR study of novel 2-aminothiazol-4(5H)-one derivatives as 11β-HSD1 inhibitors.Journal of computer-aided molecular design · 2025Article
- Screening of immune-related secretory proteins linking chronic kidney disease with calcific aortic valve disease based on comprehensive bioinformatics analysis and machine learning.Journal of translational medicine · 2023Article
- Intestinal Lymphatic Dysfunction in Kidney Disease.Circulation research · 2023Review
- Treatment with fibroblast growth factor 19 increases skeletal muscle fiber size, ameliorates metabolic perturbations and hepatic inflammation in 5/6 nephrectomized mice.Scientific reports · 2023Article
- Cardiac metabolic remodelling in chronic kidney disease.Nature reviews. Nephrology · 2022Review
- Hepatic cysteine sulphinic acid decarboxylase depletion and defective taurine metabolism in a rat partial nephrectomy model of chronic kidney disease.BMC nephrology · 2021Article
- Changes of miR-155 expression in serum of uremic patients before and after treatment and risk factors analysis.Experimental and therapeutic medicine · 2020Article
- Serum Endocannabinoid Levels in Patients With End-Stage Renal Disease.Journal of the Endocrine Society · 2019Article
- Sodium butyrate ameliorates insulin resistance and renal failure in CKD rats by modulating intestinal permeability and mucin expression.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2019Article
- Glucocorticoid activation by 11β-hydroxysteroid dehydrogenase enzymes in relation to inflammation and glycaemic control in chronic kidney disease: A cross-sectional study.Clinical endocrinology · 2019Article
- Metabolic Abnormalities in Diabetes and Kidney Disease: Role of Uremic Toxins.Current diabetes reports · 2018Review
- Lower Renal Function Is Associated With Derangement of 11-Journal of the Endocrine Society · 2018Article
- Meglitinides increase the risk of hypoglycemia in diabetic patients with advanced chronic kidney disease: a nationwide, population-based study.Oncotarget · 2017Article
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
Abstract
Insulin resistance and associated metabolic sequelae are common in chronic kidney disease (CKD) and are positively and independently associated with increased cardiovascular mortality. However, the pathogenesis has yet to be fully elucidated. 11β-Hydroxysteroid dehydrogenase type 1 (11βHSD1) catalyzes intracellular regeneration of active glucocorticoids, promoting insulin resistance in liver and other metabolic tissues. Using two experimental rat models of CKD (subtotal nephrectomy and adenine diet) which show early insulin resistance, we found that 11βHSD1 mRNA and protein increase in hepatic and adipose tissue, together with increased hepatic 11βHSD1 activity. This was associated with intrahepatic but not circulating glucocorticoid excess, and increased hepatic gluconeogenesis and lipogenesis. Oral administration of the 11βHSD inhibitor carbenoxolone to uremic rats for 2 wk improved glucose tolerance and insulin sensitivity, improved insulin signaling, and reduced hepatic expression of gluconeogenic and lipogenic genes. Furthermore, 11βHSD1(-/-) mice and rats treated with a specific 11βHSD1 inhibitor (UE2316) were protected from metabolic disturbances despite similar renal dysfunction following adenine experimental uremia. Therefore, we demonstrate that elevated hepatic 11βHSD1 is an important contributor to early insulin resistance and dyslipidemia in uremia. Specific 11βHSD1 inhibitors potentially represent a novel therapeutic approach for management of insulin resistance in patients with CKD.
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