ArticleInternational journal of biological sciences2020
Highly bioavailable Berberine formulation improves Glucocorticoid Receptor-mediated Insulin Resistance
Article in International journal of biological sciences, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 16 citations in OpenAlex.
- The Clinical Efficacy of Gegen Qinlian Decoction in Treating Type 2 Diabetes is Positively Correlated with the Dose ofDrug design, development and therapy · 2024Trial
- Article
- Calcium dynamics unplugged: NCLX in disease and therapeutic frontiers.Molecular biology reports · 2025Review
- Beneficial effects of berberine in the treatment of diabetes and its complications.Frontiers in pharmacology · 2025Review
- Molecular mechanisms, targets and clinical potential of berberine in regulating metabolism: a review focussing on databases and molecular docking studies.Frontiers in pharmacology · 2024Review
- Developmental toxicity and programming alterations of multiple organs in offspring induced by medication during pregnancy.Acta pharmaceutica Sinica. B · 2023Review
- Signaling pathways in obesity: mechanisms and therapeutic interventions.Signal transduction and targeted therapy · 2022Review
- Network Pharmacology and Bioinformatics Methods Reveal the Mechanism of Berberine in the Treatment of Ischaemic Stroke.Evidence-based complementary and alternative medicine : eCAM · 2022Article
- Therapeutic Screening of Herbal Remedies for the Management of Diabetes.Molecules (Basel, Switzerland) · 2021Review
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Authors and funding
9 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Excess glucocorticoid (GC) production is known to induce obesity and insulin resistance through increased activation of the glucocorticoid receptor (GR). The molecular mechanism for the non-genomic effects of excessive circulating GC on the insulin-signalling pathway in skeletal muscle is unknown. The plant alkaloid berberine has been shown to attenuate insulin resistance and inhibit gluconeogenesis in type 2 diabetic animals. A highly bioavailable berberine formulation termed Huang-Gui solid dispersion (HGSD), is a preparation of berberine coupled to sodium caprate and this markedly improving berberines bioavailability. Here we examined how HGSD treatment attenuated GR-mediated alteration in PI3K signalling and insulin resistance in diabetic rats, dexamethasone-treated mice and in insulin resistant C2C12 skeletal muscle cells. Blood glucose and skeletal muscle GC levels were increased and insulin signalling impaired in skeletal muscle of type 2 diabetic rats compared to controls. Treatment of these animals with HGSD restored blood glucose and skeletal muscle GC levels to that of controls. Insulin resistant C2C12 skeletal muscle cells exhibited impaired insulin signalling compared to controls and treatment of HGSD and RU486, an antagonist of GR, restored insulin signalling to that of control cells. Administration of dexamethasone to mice increased GR/GRα-associated PI3K and reduced IRS1-associated PI3K, phosphorylated-AKT, and membrane GLUT4 translocation resulting in a higher blood glucose concentration compared to controls. HGSD treatment of these mice improved insulin resistance by reducing the association of GR/GRα with PI3K. Excess GC-induced insulin resistance is mediated by increased association of GR with PI3K and treatment with HGSD attenuates these effects. We hypothesize that HGSD may be a promising candidate drug for the treatment of type 2 diabetes by reducing the association of GR with PI3K in skeletal muscle.
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