ArticleEndocrine2018
Berberine promotes glucose uptake and inhibits gluconeogenesis by inhibiting deacetylase SIRT3.
Article in Endocrine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.
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Who cites it
28 citing papers in PubMed, 1 synthesis or guideline pooled it, 47 citations in OpenAlex.
- Biochemical changes associated with non-alcoholic fatty liver disease in response to berberine treatment: a systematic review and meta-analysis of clinical and preclinical research.Frontiers in pharmacology · 2025Pooled it
- SIRT3-Dependent Actions of Berberine: From Molecular Therapies to Toxicity.Journal of biochemical and molecular toxicology · 2026Review
- Berberine: A Rising Star in the Management of Type 2 Diabetes-Novel Insights into Its Anti-Inflammatory, Metabolic, and Epigenetic Mechanisms.Pharmaceuticals (Basel, Switzerland) · 2025Review
- The role of AMPK signaling pathway in the pathogenesis of type 2 diabetes mellitus with its complications and related metabolic disorders.Metabolism open · 2025Review
- A Narrative Review on Plant Extracts for Metabolic Syndrome: Efficacy, Safety, and Technological Advances.Nutrients · 2025Review
- Pharmacological properties and therapeutic potential of berberine: a comprehensive review.Frontiers in pharmacology · 2025Review
- Article
- Article
- Definition of the Neurotoxicity-Associated Metabolic Signature Triggered by Berberine and Other Respiratory Chain Inhibitors.Antioxidants (Basel, Switzerland) · 2023Article
- Berberine Induces Mitophagy through Adenosine Monophosphate-Activated Protein Kinase and Ameliorates Mitochondrial Dysfunction in PINK1 Knockout Mouse Embryonic Fibroblasts.International journal of molecular sciences · 2023Article
- Review
- Berberine inhibits gluconeogenesis in spontaneous diabetic rats by regulating the AKT/MAPK/NO/cGMP/PKG signaling pathway.Molecular and cellular biochemistry · 2023Article
- A Review ofMolecules (Basel, Switzerland) · 2023Review
- Berberine-A Promising Therapeutic Approach to Polycystic Ovary Syndrome in Infertile/Pregnant Women.Life (Basel, Switzerland) · 2023Review
- Extracellular matrix metalloproteinase inducer in brain ischemia and intracerebral hemorrhage.Frontiers in immunology · 2022Review
- Research progress on the pharmacological effects of berberine targeting mitochondria.Frontiers in endocrinology · 2022Review
- The mechanism of berberine alleviating metabolic disorder based on gut microbiome.Frontiers in cellular and infection microbiology · 2022Review
- SL010110, a lead compound, inhibits gluconeogenesis via SIRT2-p300-mediated PEPCK1 degradation and improves glucose homeostasis in diabetic mice.Acta pharmacologica Sinica · 2021Article
- Review
- Berberine Regulated miR150-5p to Inhibit P2X7 Receptor, EMMPRIN and MMP-9 Expression in oxLDL Induced Macrophages.Frontiers in pharmacology · 2021Article
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveMany studies have confirmed the glucose-lowering effect of berberine in type 2 diabetes patients. Although the mechanism of action of berberine involves the improvement of insulin sensitivity, its hypoglycemic mechanism remains elusive. Here we show a new mechanism by which berberine antagonizes glucagon signaling and find that SIRT3 is involved in the hypoglycemic effect of berberine.
methodsGene knockout and overexpression were used to assess the inhibitory effect of berberine on SIRT3. Downstream signaling pathways and the hypoglycemic effect of SIRT3 were evaluated by immunoblotting and metabolic monitoring.
resultsWe found that berberine led to mitochondrial dysfunction and AMP accumulation by inhibiting deacetylase SIRT3. We confirmed that AMP accumulation activated the AMPK signaling pathway and further promoted glucose uptake. Simultaneously, AMP accumulation reduced cyclic AMP (cAMP) levels and abrogated the phosphorylation of critical protein targets of protein kinase A (PKA). Furthermore, we found that phosphoenolpyruvate carboxykinase 1 (PEPCK1) is a key gluconeogenesis enzyme that can be stabilized by glucagon. Berberine caused significant PEPCK1 ubiquitination and degradation by antagonizing glucagon and was accompanied by high levels of PEPCK1 acetylation. Interestingly, berberine-induced glucagon inhibition is independent of AMPK activation. The in vivo data from sirt3 knockout mice were further confirmed by the in vitro experiments.
conclusionsBerberine promotes glucose uptake and inhibits gluconeogenesis by inhibiting SIRT3, and regulating mitochondria-related pathways may provide a novel approach to the development of antidiabetic drugs.
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