ArticleThe Journal of clinical investigation2019
Dexamethasone-induced Krüppel-like factor 9 expression promotes hepatic gluconeogenesis and hyperglycemia.
Article in The Journal of clinical investigation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers.
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Who cites it
84 citing papers in PubMed, 128 citations in OpenAlex.
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- Regulatory roles and translational potential of the Kruppel-like factor family in liver disease.iLIVER · 2026Review
- Hypothalamic Control of Liver Health and Disease: From Circuits to Pathophysiology and Therapies.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
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- Chemomechanical remodeling of glucocorticoid-sensitive fibroblasts for multimodal synergistic therapy of skin fibrosis.Cell reports. Medicine · 2026Article
- Hepatic Glucocorticoid Receptor Action and Glucose Homeostasis.Endocrine reviews · 2026Review
- Multi-Omics Identification of Key Immune Molecules in Gestational Diabetes Mellitus: FKBP5 and HLA-DQA1 as Candidate Biomarkers.International journal of general medicine · 2026Article
- Comprehensive management of hematopoietic stem cell transplantation complications: from infection prevention to immune microenvironment reconstruction.Frontiers in immunology · 2026Review
- The roles, mechanisms, and therapeutic implications of glucocorticoids in glucose and lipid metabolism.Military Medical Research · 2026Review
- Bidirectional regulation of liver sinusoidal clearance by amino acid nanofibers and IGFBP4 complex: effects on HbA1c.Journal of nanobiotechnology · 2025Article
- Chronic stress, gut microbiota, and immunity: interconnections and implications for health.Molecular and cellular biochemistry · 2025Review
- Constitutive expression of cardiomyocyte Klf9 precipitates metabolic dysfunction and spontaneous cardiomyopathy.Cellular signalling · 2025Article
- Hepatic KLF9 Deficiency Inhibits Dehydroepiandrosterone (DHEA)-Induced Polycystic Ovary Syndrome via Liver-Ovary Axis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Blood Glucose and Triglyceride Changes Following the Administration of Commercial Enteral Nutrition Solutions with Differing Glucose and Fat Contents.Journal of the ASEAN Federation of Endocrine Societies · 2025Article
- GW8510 alleviates muscle atrophy and skeletal muscle dysfunction in mice through AMPK/PGC1α signaling.International journal of molecular medicine · 2025Article
- Hub biomarkers and their clinical relevance in glycometabolic disorders: A comprehensive bioinformatics and machine learning approach.Chinese medical journal · 2025Article
- Klf9 Loss of Function Protects Against Glucocorticoids Induced Skeletal Muscle Wasting.Journal of cachexia, sarcopenia and muscle · 2025Article
24 more citing papers are in PubMed but not listed here.
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Authors and funding
20 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Chronic glucocorticoid therapy has serious side effects, including diabetes and fatty liver. However, the molecular mechanisms responsible for steroid-induced diabetes remain largely enigmatic. Here, we show that hepatic Krüppel-like factor 9 (Klf9) gene expression is induced by dexamethasone and fasting. The overexpression of Klf9 in primary hepatocytes strongly stimulated Pgc1a gene expression through direct binding to its promoter, thereby activating the gluconeogenic program. However, Klf9 mutation abolished the stimulatory effect of dexamethasone on cellular glucose output. Adenovirus-mediated overexpression of KLF9 in the mouse liver markedly increased blood glucose levels and impaired glucose tolerance. Conversely, both global Klf9-mutant mice and liver-specific Klf9-deleted mice displayed fasting hypoglycemia. Moreover, the knockdown of Klf9 in the liver in diabetic mouse models, including ob/ob and db/db mice, markedly lowered fasting blood glucose levels. Notably, hepatic Klf9 deficiency in mice alleviated hyperglycemia induced by chronic dexamethasone treatment. These results suggest a critical role for KLF9 in the regulation of hepatic glucose metabolism and identify hepatic induction of KLF9 as a mechanism underlying glucocorticoid therapy-induced diabetes.
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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.