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Mechanisms for antidiabetic effect of gingerol in cultured cells and obese diabetic model mice

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Abstract

There have been studies on health beneficial effects of ginger and its components. However, there still remain certain aspects that are not well defined in their anti-hyperglycemic effects. Our aims were to find evidence of possible mechanisms for antidiabetic action of [6]-gingerol, a pungent component of ginger, employing a rat skeletal muscle-derived cell line, a rat-derived pancreatic β-cell line, and type 2 diabetic model animals. The antidiabetic effect of [6]-gingerol was investigated through studies on glucose uptake in L6 myocytes and on pancreatic β-cell protective ability from reactive oxygen species (ROS) in RIN-5F cells. Its in vivo effect was also examined using obese diabetic db/db mice. [6]-Gingerol increased glucose uptake under insulin absent condition and induced 5′ adenosine monophosphate-activated protein kinase phosphorylation in L6 myotubes. Promotion by [6]-gingerol of glucose transporter 4 (GLUT4) translocation to plasma membrane was visually demonstrated by immunocytochemistry in L6 myoblasts transfected with glut4 cDNA-coding vector. [6]-Gingerol suppressed advanced glycation end product-induced rise of ROS levels in RIN-5F pancreatic β-cells. [6]-Gingerol feeding suppressed the increases in fasting blood glucose levels and improved glucose intolerance in db/db mice. [6]-Gingerol regulated hepatic gene expression of enzymes related to glucose metabolism toward decreases in gluconeogenesis and glycogenolysis as well as an increase in glycogenesis, thereby contributing to reductions in hepatic glucose production and hence blood glucose concentrations. These in vitro and in vivo results strongly suggest that [6]-gingerol has antidiabetic potential through multiple mechanisms.

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Abbreviations

AMPK:

5′ Adenosine monophosphate-activated protein kinase

GLUT4:

Glucose transporter 4

G6Pase:

Glucose-6-phosphatase

GS:

Glycogen synthase

LGP:

Liver glycogen phosphorylase

PEPCK:

Phosphoenolpyruvate carboxykinase

TBARS:

Thiobarbituric acid-reactive substances

TC:

Total cholesterol

TG:

Triglyceride

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Acknowledgments

This work was supported in part by the Japan Science Society and in part by the Asahi Group Foundation, Tokyo, Japan.

Conflict of interest

Authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Applied Life Science, Graduate School of Agricultural Science, Tokyo University of Agriculture and Technology, Fuchu, Tokyo, 183-8509, Japan

    Myoung Jin Son

  2. Division of Applied Biological Chemistry, Institute of Agriculture, Tokyo University of Agriculture and Technology, Fuchu, Tokyo, 183-8509, Japan

    Yutaka Miura & Kazumi Yagasaki

Authors
  1. Myoung Jin Son
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  2. Yutaka Miura
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  3. Kazumi Yagasaki
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Correspondence to Kazumi Yagasaki.

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Son, M.J., Miura, Y. & Yagasaki, K. Mechanisms for antidiabetic effect of gingerol in cultured cells and obese diabetic model mice. Cytotechnology 67, 641–652 (2015). https://doi.org/10.1007/s10616-014-9730-3

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