ArticleThe Journal of biological chemistry2012
Orphan nuclear receptor small heterodimer partner negatively regulates growth hormone-mediated induction of hepatic gluconeogenesis through inhibition of signal transducer and activator of transcription 5 (STAT5) transactivation.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 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
23 citing papers in PubMed, 42 citations in OpenAlex.
- Endocrine regulation of the hepatic fasting response: cues, cooperation and consequences.Nature reviews. Endocrinology · 2026Review
- Integrating bile acid metabolism into precision nutrition strategies for improved swine performance.Animal nutrition (Zhongguo xu mu shou yi xue hui) · 2026Review
- Research progress in abnormal carbohydrate, lipid, and protein metabolism in children with isolated growth hormone deficiency.Frontiers in endocrinology · 2025Review
- Emerging roles of cytosolic phosphoenolpyruvate kinase 1 (PCK1) in cancer.Biochemistry and biophysics reports · 2023Review
- Enhancement of the SESN2-SHP cascade by melatonin ameliorates hepatic gluconeogenesis by inhibiting the CRBN-BTG2-CREBH signaling pathway.Experimental & molecular medicine · 2023Article
- Review
- Growth hormone promotes hepatic gluconeogenesis by enhancing BTG2-YY1 signaling pathway.Scientific reports · 2021Article
- Bile acid receptors FXR and TGR5 signaling in fatty liver diseases and therapy.American journal of physiology. Gastrointestinal and liver physiology · 2020Review
- Microbial Metabolites: Critical Regulators in NAFLD.Frontiers in microbiology · 2020Review
- Loss of growth hormone-mediated signal transducer and activator of transcription 5 (STAT5) signaling in mice results in insulin sensitivity with obesity.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- B-cell translocation gene 2 enhances fibroblast growth factor 21 production by inducing Kruppel-like factor 15.Scientific reports · 2019Article
- Physiological changes of growth hormone during lactation in pup rats artificially reared.PloS one · 2019Article
- Differential tissue response to growth hormone in mice.FEBS open bio · 2018Article
- Effects of growth hormone on glucose metabolism and insulin resistance in human.Annals of pediatric endocrinology & metabolism · 2017Review
- G-protein-coupled bile acid receptor plays a key role in bile acid metabolism and fasting-induced hepatic steatosis in mice.Hepatology (Baltimore, Md.) · 2017Article
- Small Heterodimer Partner (NR0B2) Coordinates Nutrient Signaling and the Circadian Clock in Mice.Molecular endocrinology (Baltimore, Md.) · 2016Article
- Disruption of STAT5b-Regulated Sexual Dimorphism of the Liver Transcriptome by Diverse Factors Is a Common Event.PloS one · 2016Article
- Article
- Metformin activates AMP-activated protein kinase by promoting formation of the αβγ heterotrimeric complex.The Journal of biological chemistry · 2015Article
- Minireview: mechanisms of growth hormone-mediated gene regulation.Molecular endocrinology (Baltimore, Md.) · 2014Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 5 institutions in 2 countries.
Funding
Abstract
Growth hormone (GH) is a key metabolic regulator mediating glucose and lipid metabolism. Ataxia telangiectasia mutated (ATM) is a member of the phosphatidylinositol 3-kinase superfamily and regulates cell cycle progression. The orphan nuclear receptor small heterodimer partner (SHP: NR0B2) plays a pivotal role in regulating metabolic processes. Here, we studied the role of ATM on GH-dependent regulation of hepatic gluconeogenesis in the liver. GH induced phosphoenolpyruvate carboxykinase (PEPCK) and glucose 6-phosphatase gene expression in primary hepatocytes. GH treatment and adenovirus-mediated STAT5 overexpression in hepatocytes increased glucose production, which was blocked by a JAK2 inhibitor, AG490, dominant negative STAT5, and STAT5 knockdown. We identified a STAT5 binding site on the PEPCK gene promoter using reporter assays and point mutation analysis. Up-regulation of SHP by metformin-mediated activation of the ATM-AMP-activated protein kinase pathway led to inhibition of GH-mediated induction of hepatic gluconeogenesis, which was abolished by an ATM inhibitor, KU-55933. Immunoprecipitation studies showed that SHP physically interacted with STAT5 and inhibited STAT5 recruitment on the PEPCK gene promoter. GH-induced hepatic gluconeogenesis was decreased by either metformin or Ad-SHP, whereas the inhibition by metformin was abolished by SHP knockdown. Finally, the increase of hepatic gluconeogenesis following GH treatment was significantly higher in the liver of SHP null mice compared with that of wild-type mice. Overall, our results suggest that the ATM-AMP-activated protein kinase-SHP network, as a novel mechanism for regulating hepatic glucose homeostasis via a GH-dependent pathway, may be a potential therapeutic target for insulin resistance.
Indexed as
Identifiers
What OpenQuestion holds
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.