European Journal of Nutrition

, Volume 52, Issue 6, pp 1607–1619

Aspalathin improves hyperglycemia and glucose intolerance in obese diabetic ob/ob mice

  • Myoung Jin Son
  • Miki Minakawa
  • Yutaka Miura
  • Kazumi Yagasaki
Original Contribution

DOI: 10.1007/s00394-012-0466-6

Cite this article as:
Son, M.J., Minakawa, M., Miura, Y. et al. Eur J Nutr (2013) 52: 1607. doi:10.1007/s00394-012-0466-6



Although several researches have demonstrated that rooibos extract has hypoglycemic effect, the role of aspalathin, a main polyphenol in the extract, remains unclear. Our aims were to find specific mechanisms for anti-diabetic action of aspalathin employing a rat skeletal muscle-derived cell line (L6 myocytes) and a rat-derived pancreatic β-cell line (RIN-5F cells) and to investigate its effect in type 2 diabetic model ob/ob mice.


We investigated in vitro the effect of aspalathin on the glucose metabolism through the studies on molecular mechanisms of glucose uptake using cultured L6 myotubes. We also measured the antioxidative ability of aspalathin against reactive oxygen species (ROS) generated by artificial advanced glycation end product (AGE) in RIN-5F cells. In vivo, ob/ob mice were fed 0.1 % aspalathin-containing diet for 5 weeks, and the effect of aspalathin on fasting blood glucose level, glucose intolerance, and hepatic gene expression was studied.


Aspalathin dose dependently increased glucose uptake by L6 myotubes and promoted AMP-activated protein kinase (AMPK) phosphorylation. Aspalathin enhanced GLUT4 translocation to plasma membrane in L6 myoblasts and myotubes. In RIN-5F cells, aspalathin suppressed AGE-induced rises in ROS. In vivo, aspalathin significantly suppressed the increase in fasting blood glucose levels and improved glucose intolerance. Furthermore, aspalathin decreased expression of hepatic genes related to gluconeogenesis and lipogenesis.


Hypoglycemic effect of aspalathin is related to increased GLUT4 translocation to plasma membrane via AMPK activation. In addition, aspalathin reduces the gene expression of hepatic enzymes related to glucose production and lipogenesis. These results strongly suggest that aspalathin has anti-diabetic potential.


AspalathinAMPKGLUT4 translocationHyperglycemiaAdvanced glycation end products (AGEs)



Phosphoenolpyruvate carboxykinase




Glycogen synthase


Liver glycogen phosphorylase


Acetyl-CoA carboxylase


Fatty acid synthase


Stearoyl-CoA desaturase 1


Adenosine monophosphate-activated protein kinase


Glucose transporter 4

Supplementary material

394_2012_466_MOESM1_ESM.ppt (151 kb)
Supplementary material 1 (PPT 151 kb)

Copyright information

© Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  • Myoung Jin Son
    • 1
  • Miki Minakawa
    • 1
  • Yutaka Miura
    • 2
  • Kazumi Yagasaki
    • 2
    • 3
  1. 1.Department of Applied Life Science, Graduate School of Agricultural ScienceTokyo University of Agriculture and TechnologyFuchuJapan
  2. 2.Division of Applied Biological Chemistry, Institute of AgricultureTokyo University of Agriculture and TechnologyFuchuJapan
  3. 3.Graduate School of MedicineThe University of TokyoBunkyo-KuJapan