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Updated: Jul 5, 2025

Measurement of Insulin- and Contraction-Stimulated Glucose Uptake in Isolated and Incubated Mature Skeletal Muscle from Mice
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Two Prenylated Chalcones, 4-Hydroxyderricin, and Xanthoangelol Prevent Postprandial Hyperglycemia by Promoting GLUT4

Kevin Odongo1, Ayane Abe1, Rina Kawasaki1

  • 1Department of Agrobioscience, Graduate School of Agricultural Science, Kobe University, Kobe, 657-8501, Japan.

Molecular Nutrition & Food Research
|January 24, 2024
PubMed
Abstract

Insights

Ashitaba chalcones, 4-hydroxyderricin (4-HD) and xanthoangelol (XAG), enhance glucose uptake in skeletal muscle by activating the LKB1/AMPK pathway. This mechanism suppresses acute hyperglycemia, offering potential therapeutic benefits.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Pharmacology

Background:

  • Skeletal muscle glucose uptake is vital for managing postprandial hyperglycemia.
  • Insulin and polyphenols stimulate glucose uptake via glucose transporter 4 (GLUT4) translocation.
  • The molecular mechanisms of Ashitaba chalcones (4-HD, XAG) on glucose uptake are not fully understood.

Purpose of the Study:

  • To elucidate the molecular mechanism by which 4-HD and XAG enhance glucose uptake and GLUT4 translocation in L6 myotubes.
  • To confirm the antihyperglycemic effects of 4-HD and XAG in vivo.

Main Methods:

  • Investigated signaling pathways (AMPK, LKB1, PI3K/Akt, JAKs/STATs) in L6 myotubes treated with 4-HD and XAG.
  • Utilized an AMPK inhibitor (Compound C) and siRNA to block AMPK and LKB1.
  • Assessed antihyperglycemic effects in male ICR mice using an oral glucose tolerance test.

Main Results:

  • 4-HD and XAG activated the LKB1/AMPK pathway, promoting glucose uptake and GLUT4 translocation in L6 myotubes.
  • Activation of PI3K/Akt and JAKs/STATs pathways was not observed.
  • Inhibition of AMPK or LKB1 abolished the glucose uptake-enhancing effects of 4-HD and XAG.
  • Oral administration of 4-HD and XAG suppressed acute hyperglycemia in mice.

Conclusions:

  • The LKB1/AMPK signaling pathway is a key mediator of Ashitaba chalcone-induced GLUT4 translocation in skeletal muscle.
  • These findings demonstrate the antihyperglycemic potential of Ashitaba chalcones through skeletal muscle glucose uptake modulation.
Keywords:
4‐hydroxyderricinAMPKAngelica keiskei Koidzumi (Ashitaba)GLUT4xanthoangelol

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