ArticleThe Journal of clinical investigation2020
Obesity-induced excess of 17-hydroxyprogesterone promotes hyperglycemia through activation of glucocorticoid receptor.
Article in The Journal of clinical investigation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 2 of them syntheses that pooled it.
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Who cites it
31 citing papers in PubMed, 2 syntheses or guidelines pooled it, 41 citations in OpenAlex.
- Effects of rapeseed oil on body composition and glucolipid metabolism in people with obesity and overweight: a systematic review and meta-analysis.European journal of clinical nutrition · 2024Pooled it
- Effects of resistance training on body composition and physical function in elderly patients with osteosarcopenic obesity: a systematic review and meta-analysis.Archives of osteoporosis · 2022Pooled it
- Visceral adiposity and insulin resistance in polycystic ovarian syndrome - A cross-sectional, observational study.European journal of obstetrics & gynecology and reproductive biology: X · 2026Article
- The roles, mechanisms, and therapeutic implications of glucocorticoids in glucose and lipid metabolism.Military Medical Research · 2026Review
- Machine Learning-Based Prediction Model Construction for Type 2 Diabetes Mellitus: A Comparison of Algorithms and Multilevel Risk Factor Analysis.Journal of diabetes research · 2026Article
- CYP51A1 in health and disease: from sterol metabolism to regulated cell death.Cell death discovery · 2025Review
- Metabolomic analysis of rat arterial serum under hypobaric hypoxia: Adaptive regulation of physiological systems by metabolic reprogramming.Biochemistry and biophysics reports · 2025Article
- Metabolic dysfunction associated fatty liver disease and type 2 diabetes: pathophysiological links, epidemiological trends, and clinical implications.Frontiers in endocrinology · 2025Review
- Beneficial effects of berberine in the treatment of diabetes and its complications.Frontiers in pharmacology · 2025Review
- Untargeted metabolomics reveals distinct biomarkers and metabolic alterations in familial and non-genetic hypercholesterolemia in Saudi patients.Frontiers in medicine · 2025Article
- Metabolic syndrome in colorectal cancer liver metastasis: metabolic reprogramming and microenvironment crosstalk.Frontiers in immunology · 2025Review
- Holothoracic spinal epidural lipomatosis: Report of a rare presentation and review of literature.SAGE open medical case reports · 2025Article
- OSGEP regulates islet β-cell function by modulating proinsulin translation and maintaining ER stress homeostasis in mice.Nature communications · 2024Article
- Glucocorticoid Receptor Antagonism Improves Glucose Metabolism in a Mouse Model of Polycystic Ovary Syndrome.Journal of the Endocrine Society · 2023Article
- Mutated CYP17A1 promotes atherosclerosis and early-onset coronary artery disease.Cell communication and signaling : CCS · 2023Article
- Time-Dependent Changes in the Bladder Muscle Metabolome After Traumatic Spinal Cord Injury in Rats Using Metabolomics.International neurourology journal · 2023Article
- The Role of Steroidomics in the Diagnosis of Alzheimer's Disease and Type 2 Diabetes Mellitus.International journal of molecular sciences · 2023Article
- Type 2 diabetes originated from non-alcoholic fatty liver disease.Life metabolism · 2023Review
- Association of sex hormones and sex hormone-binding globulin with liver fat in men and women: an observational and Mendelian randomization study.Frontiers in endocrinology · 2023Observational
- Cortisol and cardiometabolic disease: a target for advancing health equity.Trends in endocrinology and metabolism: TEM · 2022Review
Corrections and comments
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Authors and funding
18 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Type 2 diabetes mellitus (T2DM) has become an expanding global public health problem. Although the glucocorticoid receptor (GR) is an important regulator of glucose metabolism, the relationship between circulating glucocorticoids (GCs) and the features of T2DM remains controversial. Here, we show that 17-hydroxyprogesterone (17-OHP), an intermediate steroid in the biosynthetic pathway that converts cholesterol to cortisol, binds to and stimulates the transcriptional activity of GR. Hepatic 17-OHP concentrations are increased in diabetic mice and patients due to aberrantly increased expression of Cyp17A1. Systemic administration of 17-OHP or overexpression of Cyp17A1 in the livers of lean mice promoted the pathogenesis of hyperglycemia and insulin resistance, whereas knockdown of Cyp17A1 abrogated metabolic disorders in obese mice. Therefore, our results identify a Cyp17A1/17-OHP/GR-dependent pathway in the liver that mediates obesity-induced hyperglycemia, suggesting that selectively targeting hepatic Cyp17A1 may provide a therapeutic avenue for treating T2DM.
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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.