Anti-diabetic phytochemicals that promote GLUT4 translocation via AMPK signaling in muscle cells

Abstract

Skeletal muscles are the largest tissue in our body and play an important role in maintaining glucose homeostasis. Cultured L6 myotubes and C2C12 myotubes are useful to construct simple glucose uptake assay systems, to screen various phytochemicals that promote glucose uptake, and to clarify their modes of actions. In skeletal muscles, insulin promotes glucose uptake by activating phosphatidylinositol-3 kinase (PI3K) and Akt, leading to increased translocation of glucose transporter 4 (GLUT4) to the plasma membrane. Another GLUT4 translocation promoter is 5′ adenosine monophosphate-activated protein kinase (AMPK). In mammalian cells, AMPK activated by an increase in AMP/ATP ratio acts as an energy sensor. AMPK is activated by exercise/contraction in muscle cells and compound such as metformin, this resulting in stimulation of GLUT4 translocation to plasma membrane and hence glucose uptake in skeletal muscles. Thus, studies on novel compounds that activate skeletal muscle glucose uptake and AMPK would be useful for the development of new treatment of insulin resistance and type 2 diabetes (T2D). Here we review the current knowledge of phytochemicals in foods and beverages that promote GLUT4 translocation via AMPK signaling in muscle cells, and their effects on glucose metabolism in mainly T2D model mice. Phytochemicals that have potential to stimulate glucose uptake in muscle cells are suggested to be anti-diabetic.