ArticleNutrients2019
Glycyrrhetinic Acid Improves Insulin-Response Pathway by Regulating the Balance between the Ras/MAPK and PI3K/Akt Pathways.
Article in Nutrients, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 32 citations in OpenAlex.
- PDK1-mediated PI3K/Akt signaling regulates metabolic and developmental programs in a cosmopolitan pest.Pest management science · 2026Article
- Glycyrrhetinic acid augments lipid catabolism via immune-neural modulation in adipose tissue.Journal of advanced research · 2026Article
- Targeting the Ras-Ral Signaling Axis in Type 2 Diabetes Mellitus: A Dual-Modulation Approach to Correcting Insulin Resistance and β-Cell Dysfunction.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Influence and treatment of insulin receptor substrate/PI3K/Akt‑mediated insulin resistance in diabetes mellitus (Review).Molecular medicine reports · 2026Review
- Metabolites of traditional Chinese medicine targeting PI3K/AKT signaling pathway for hypoglycemic effect in type 2 diabetes.Frontiers in pharmacology · 2024Review
- Research status of indole-modified natural products.RSC medicinal chemistry · 2023Review
- Glucuronic acid metabolites of phenolic acids target AKT-PH domain to improve glucose metabolism.Chinese herbal medicines · 2023Article
- The protective roles of citrus flavonoids, naringenin, and naringin on endothelial cell dysfunction in diseases.Heliyon · 2023Review
- Editorial: Neurological comorbidity in metabolic syndrome.Frontiers in neuroscience · 2023Article
- Glycyrrhizic Acid and Its Derivatives: Promising Candidates for the Management of Type 2 Diabetes Mellitus and Its Complications.International journal of molecular sciences · 2022Review
- Recent Advances Regarding the Molecular Mechanisms of Triterpenic Acids: A Review (Part II).International journal of molecular sciences · 2022Review
- Effect ofPharmaceutical biology · 2021Article
- Insulin Receptor Substrate 1 Gene and Glucose Metabolism Characteristics in Type 2 Diabetes Mellitus with Comorbidities.Ethiopian journal of health sciences · 2021Article
- Indole- and Pyrazole-Glycyrrhetinic Acid Derivatives as PTP1B Inhibitors: Synthesis, In Vitro and In Silico Studies.Molecules (Basel, Switzerland) · 2021Article
- Research progress on the protective effects of licorice-derived 18β-glycyrrhetinic acid against liver injury.Acta pharmacologica Sinica · 2021Review
- Network Pharmacology-Based Strategy for Elucidating the Molecular Basis Forthe Pharmacologic Effects of Licorice (Frontiers in pharmacology · 2021Article
- Trilobatin ameliorates insulin resistance through IRS-AKT-GLUT4 signaling pathway in C2C12 myotubes and ob/ob mice.Chinese medicine · 2020Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Glycyrrhetinic acid (GA), a bioactive component in the human diet, has been reported to improve hyperglycemia, dyslipidemia, insulin resistance and obesity in rats with metabolic syndrome. However, GA-specific target proteins and the mechanisms involved in the downstream signaling and cross-talk to improve insulin sensitivity have not been fully elucidated. In this study, the potential targets of GA were identified by chemical proteomics strategies using serial GA probes for target fishing and cell molecular imaging. Intracellular enzyme activity evaluation and insulin resistance models were used for validating the function of the target proteins on the downstream insulin signaling pathways. Collectively, our data demonstrate that GA improved the insulin-responsive pathway and glucose consumption levels via multiple diabetogenic factors that activated the insulin signaling pathway in HepG2 cells. GA improved Glucose transporter 4(GLUT4) expression by targeting the Ras protein to regulate the mitogen-activated protein kinase (MAPK) pathway. GA exhibited a strong inhibitory effect on IRS1ser307 phosphorylation in cells treated with the Protein kinase C (PKC) activator Phorbol 12-myristate 13-acetate (PMA.) Consistently, IRS1ser307 phosphorylation was also inhibited by GA in Free fatty acid (FFA)-treated HepG2 cells. GA also inhibited the PMA-induced phosphorylation of IκB kinase α/β (IKKα/β), c-Jun N-terminal kinase (JNK) and p38 proteins (P38), suggesting that IKKα/β, JNK and P38 activation is dependent on PKC activity.
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