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Dayarathne LA, Ranaweera SS, Natraj P, et al. The effects of naringenin and naringin on the glucose uptake and AMPK phosphorylation in high glucose treated HepG2 cells. J Vet Sci. 2021;22(6):e92doi: 10.4142/jvs.2021.22.e92.
Dayarathne, L. A., Ranaweera, S. S., Natraj, P., Rajan, P., Lee, Y. J., & Han, C. H. (2021). The effects of naringenin and naringin on the glucose uptake and AMPK phosphorylation in high glucose treated HepG2 cells. Journal of veterinary science, 22(6), e92. https://doi.org/10.4142/jvs.2021.22.e92
Dayarathne, Lakshi A, et al. "The effects of naringenin and naringin on the glucose uptake and AMPK phosphorylation in high glucose treated HepG2 cells." Journal of veterinary science vol. 22,6 (2021): e92. doi: https://doi.org/10.4142/jvs.2021.22.e92
Dayarathne LA, Ranaweera SS, Natraj P, Rajan P, Lee YJ, Han CH. The effects of naringenin and naringin on the glucose uptake and AMPK phosphorylation in high glucose treated HepG2 cells. J Vet Sci. 2021 Nov;22(6):e92. doi: 10.4142/jvs.2021.22.e92. PMID: 34854271; PMCID: PMC8636664.
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J Vet Sci. 2021 Nov;22(6):e92. doi: 10.4142/jvs.2021.22.e92.

The effects of naringenin and naringin on the glucose uptake and AMPK phosphorylation in high glucose treated HepG2 cells.

Journal of veterinary science

Lakshi A Dayarathne, Sachithra S Ranaweera, Premkumar Natraj, Priyanka Rajan, Young Jae Lee, Chang-Hoon Han

Affiliations

  1. College of Veterinary Medicine, Jeju National University, Jeju 63243, Korea.
  2. College of Veterinary Medicine, Jeju National University, Jeju 63243, Korea. [email protected].

PMID: 34854271 PMCID: PMC8636664 DOI: 10.4142/jvs.2021.22.e92

Abstract

BACKGROUND: Naringin and its aglycone naringenin are citrus-derived flavonoids with several pharmacological effects. On the other hand, the mechanism for the anti-diabetic effects of naringenin and naringin are controversial and remain to be clarified further.

OBJECTIVE: This study examined the relationship between glucose uptake and AMP-activated protein kinase (AMPK) phosphorylation by naringenin and naringin in high glucose-treated HepG2 cells.

METHODS: Glucose uptake was measured using the 2-NBDG fluorescent D-glucose analog. The phosphorylation levels of AMPK and GSK3β (Glycogen synthase kinase 3 beta) were observed by Western blotting. Molecular docking analysis was performed to evaluate the binding affinity of naringenin and naringin to the γ-subunit of AMPK.

RESULTS: The treatment with naringenin and naringin stimulated glucose uptake regardless of insulin stimulation in high glucose-treated HepG2 cells. Both flavonoids increased glucose uptake by promoting the phosphorylation of AMPK at Thr172 and increased the phosphorylation of GSK3β. Molecular docking analysis showed that both naringenin and naringin bind to the γ-subunit of AMPK with high binding affinities. In particular, naringin showed higher binding affinity than the true modulator, AMP with all three CBS domains (CBS1, 3, and 4) in the γ-subunit of AMPK. Therefore, both naringenin and naringin could be positive modulators of AMPK activation, which enhance glucose uptake regardless of insulin stimulation in high glucose-treated HepG2 cells.

CONCLUSIONS: The increased phosphorylation of AMPK at Thr172 by naringenin and naringin might enhance glucose uptake regardless of insulin stimulation in high glucose treated HepG2 cells.

© 2021 The Korean Society of Veterinary Science.

Keywords: AMPK phosphorylation; Naringenin; glucose uptake; molecular docking; naringin

Conflict of interest statement

The authors declare no conflicts of interest.

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