ArticleScientific reports2020
Inhibition of Grb14, a negative modulator of insulin signaling, improves glucose homeostasis without causing cardiac dysfunction.
Article in Scientific reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02706262 (Complex Effects of Dietary Manipulation on Metabolic Function, Inflammation and Health), which is not on this map. Cited by 16 papers, 1 of them a synthesis that pooled it.
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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.
Complex Effects of Dietary Manipulation on Metabolic Function, Inflammation and Health
Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Molecular Effects of Physical Activity and Body Composition: A Systematic Review and Meta-Analysis.International journal of environmental research and public health · 2025Pooled it
- Small Molecule Insulin Sensitisers: New Leads and Targets for Next-Generation Insulin Sensitising Strategies.Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2026Review
- Identification of targets of clinical FOXA1 mutants involved in EMT and immune suppression in prostate cancer.Communications biology · 2026Article
- Human genetics of metabolic dysfunction-associated steatotic liver disease: from variants to cause to precision treatment.The Journal of clinical investigation · 2025Review
- GRB14: A prognostic biomarker driving tumor progression in gastric cancer through the PI3K/AKT signaling pathway by interacting with COBLL1.Open life sciences · 2025Article
- A method for finding epistatic effects of maternal and fetal variants.Frontiers in genetics · 2025Article
- Article
- The subcutaneous adipose transcriptome identifies a molecular signature of insulin resistance shared with visceral adipose.Obesity (Silver Spring, Md.) · 2024Article
- 1-L Transcription of SARS-CoV-2 Spike Protein S1 Subunit.International journal of molecular sciences · 2024Article
- The alteration of LBX1 expression is associated with changes in parameters related to energy metabolism in mice.PloS one · 2024Article
- A whole-genome reference panel of 14,393 individuals for East Asian populations accelerates discovery of rare functional variants.Science advances · 2023Article
- Current Studies on Molecular Mechanisms of Insulin Resistance.Journal of diabetes research · 2022Review
- Dynamic changes of plasma extracellular vesicle long RNAs during perioperative period of colorectal cancer.Bioengineered · 2021Article
- Investigation of candidate genes and mechanisms underlying obesity associated type 2 diabetes mellitus using bioinformatics analysis and screening of small drug molecules.BMC endocrine disorders · 2021Article
- Importance of Adipose Tissue NAD+ Biology in Regulating Metabolic Flexibility.Endocrinology · 2021Article
- Sustained Stimulation of βDiabetes, metabolic syndrome and obesity : targets and therapy · 2020Article
Corrections and comments
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12 authors.
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Abstract
Insulin resistance increases patients' risk of developing type 2 diabetes (T2D), non-alcoholic steatohepatitis (NASH) and a host of other comorbidities including cardiovascular disease and cancer. At the molecular level, insulin exerts its function through the insulin receptor (IR), a transmembrane receptor tyrosine kinase. Data from human genetic studies have shown that Grb14 functions as a negative modulator of IR activity, and the germline Grb14-knockout (KO) mice have improved insulin signaling in liver and skeletal muscle. Here, we show that Grb14 knockdown in liver, white adipose tissues, and heart with an AAV-shRNA (Grb14-shRNA) improves glucose homeostasis in diet-induced obese (DIO) mice. A previous report has shown that germline deletion of Grb14 in mice results in cardiac hypertrophy and impaired systolic function, which could severely limit the therapeutic potential of targeting Grb14. In this report, we demonstrate that there are no significant changes in cardiac function as measured by echocardiography in the Grb14-knockdown mice fed a high-fat diet for a period of four months. While additional studies are needed to further confirm the efficacy and to de-risk potential negative cardiac effects in preclinical models, our data support the therapeutic strategy of inhibiting Grb14 to treat diabetes and related conditions.
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