ArticleMolecular metabolism2020
Activation of SIK1 by phanginin A inhibits hepatic gluconeogenesis by increasing PDE4 activity and suppressing the cAMP signaling pathway.
Article in Molecular metabolism, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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14 citing papers in PubMed, 34 citations in OpenAlex.
- Activation of SIK1 by phanginin A regulates skeletal muscle glucose uptake by phosphorylating HADC4/5/7 and enhancing GLUT4 expression and translocation.Natural products and bioprospecting · 2025Article
- Evaluation of Hypoglycemic Polyphenolic Compounds in Blueberry Extract: Functional Effects and Mechanisms.Antioxidants (Basel, Switzerland) · 2024Article
- Manual Therapy Improves Fibromyalgia Symptoms by DownregulatingInternational journal of molecular sciences · 2024Observational
- Understanding the roles of salt-inducible kinases in cardiometabolic disease.Frontiers in physiology · 2024Review
- Unveiling the Role of Sik1 in Osteoblast Differentiation: Implications for Osteoarthritis.Molecular and cellular biology · 2024Article
- Deficiency of salt-inducible kinase 2 (SIK2) promotes immune injury by inhibiting the maturation of lymphocytes.MedComm · 2023Article
- FAM3D inhibits gluconeogenesis in high glucose environment via DUSP1/ZFP36/SIK1 axis.The Kaohsiung journal of medical sciences · 2023Article
- Coronarin A modulated hepatic glycogen synthesis and gluconeogenesis via inhibiting mTORC1/S6K1 signaling and ameliorated glucose homeostasis of diabetic mice.Acta pharmacologica Sinica · 2023Article
- Article
- The Effects of Antioxidants from Natural Products on Obesity, Dyslipidemia, Diabetes and Their Molecular Signaling Mechanism.International journal of molecular sciences · 2022Review
- Integration of Lipidomics and Transcriptomics Reveals the Efficacy and Mechanism of Qige Decoction on NAFLD.Evidence-based complementary and alternative medicine : eCAM · 2022Article
- SL010110, a lead compound, inhibits gluconeogenesis via SIRT2-p300-mediated PEPCK1 degradation and improves glucose homeostasis in diabetic mice.Acta pharmacologica Sinica · 2021Article
- Review
- HDAC4 Knockdown Alleviates Denervation-Induced Muscle Atrophy by Inhibiting Myogenin-Dependent Atrogene Activation.Frontiers in cellular neuroscience · 2021Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveSalt-induced kinase 1 (SIK1) acts as a key modulator in many physiological processes. However, the effects of SIK1 on gluconeogenesis and the underlying mechanisms have not been fully elucidated. In this study, we found that a natural compound phanginin A could activate SIK1 and further inhibit gluconeogenesis. The mechanisms by which phanginin A activates SIK1 and inhibits gluconeogenesis were explored in primary mouse hepatocytes, and the effects of phanginin A on glucose homeostasis were investigated in ob/ob mice.
methodsThe effects of phanginin A on gluconeogenesis and SIK1 phosphorylation were examined in primary mouse hepatocytes. Pan-SIK inhibitor and siRNA-mediated knockdown were used to elucidate the involvement of SIK1 activation in phanginin A-reduced gluconeogenesis. LKB1 knockdown was used to explore how phanginin A activated SIK1. SIK1 overexpression was used to evaluate its effect on gluconeogenesis, PDE4 activity, and the cAMP pathway. The acute and chronic effects of phanginin A on metabolic abnormalities were observed in ob/ob mice.
resultsPhanginin A significantly increased SIK1 phosphorylation through LKB1 and further suppressed gluconeogenesis by increasing PDE4 activity and inhibiting the cAMP/PKA/CREB pathway in primary mouse hepatocytes, and this effect was blocked by pan-SIK inhibitor HG-9-91-01 or siRNA-mediated knockdown of SIK1. Overexpression of SIK1 in hepatocytes increased PDE4 activity, reduced cAMP accumulation, and thereby inhibited gluconeogenesis. Acute treatment with phanginin A reduced gluconeogenesis in vivo, accompanied by increased SIK1 phosphorylation and PDE4 activity in the liver. Long-term treatment of phanginin A profoundly reduced blood glucose levels and improved glucose tolerance and dyslipidemia in ob/ob mice.
conclusionWe discovered an unrecognized effect of phanginin A in suppressing hepatic gluconeogenesis and revealed a novel mechanism that activation of SIK1 by phanginin A could inhibit gluconeogenesis by increasing PDE4 activity and suppressing the cAMP/PKA/CREB pathway in the liver. We also highlighted the potential value of phanginin A as a lead compound for treating type 2 diabetes.
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