Epigallocatechin gallate induces GLUT4 translocation in skeletal muscle through both PI3K- and AMPK-dependent pathways

• Published in: Food & function 2018-08, Vol.9 (8), p.4223-4233
• Main Authors: Ueda-Wakagi, Manabu, Hayashibara, Kaori, Nagano, Tomoya, Ikeda, Masaki, Yuan, Sihao, Ueda, Shuji, Shirai, Yasuhito, Yoshida, Ken-ichi, Ashida, Hitoshi
• Format: Article
• Language: English
• Subjects: 1-Phosphatidylinositol 3-kinase; Accumulation; Actin; Adenosine kinase; Adenosine monophosphate; AKT protein; AMP; AMP-Activated Protein Kinases - genetics; AMP-Activated Protein Kinases - metabolism; Animals; Catechin - analogs & derivatives; Catechin - pharmacology; Cell Line; Cell Membrane; Downstream effects; Epigallocatechin gallate; Gene Expression Regulation - drug effects; Glucose; Glucose - metabolism; Glucose transporter; Glucose Transporter Type 4 - metabolism; Glycogen; Hyperglycemia; Insulin; Isoenzymes - metabolism; Kinases; Laminin; Male; Mice; Mice, Inbred ICR; Mode of action; Muscle, Skeletal - drug effects; Muscle, Skeletal - metabolism; Muscles; Musculoskeletal system; Oral administration; Phosphatidylinositol 3-Kinases - genetics; Phosphatidylinositol 3-Kinases - metabolism; Phosphorylation; Protein kinase C; Protein Kinase C - metabolism; Protein Transport - drug effects; Proteins; Rac1 protein; Ribonucleic acid; RNA; RNA-mediated interference; Skeletal muscle; Translocation
• ISSN: 2042-6496; 2042-650X
• DOI: 10.1039/c8fo00807h

Our previous report demonstrated that epigallocatechin gallate (EGCg) promotes translocation of glucose transporter 4 (GLUT4) in skeletal muscle. In this study, we investigated the molecular mechanism of GLUT4 translocation by EGCg at the physiological concentration range. In L6 cells, EGCg induced phosphorylation of phosphatidylinositide 3′-kinase (PI3K) and downstream protein kinase C (PKC) λ/ξ without affecting the phosphorylation of insulin receptor and Akt. EGCg-induced GLUT4 translocation was suppressed by RNA interference-mediated knockdown of PI3K and treatment with PKC inhibitor Go6983. Moreover, EGCg increased Rac1 activity and actin remodelling as downstream events of PKCλ/ξ. These results indicate that EGCg induced GLUT4 translocation through a PI3K-dependent pathway, but its mode of action differed from that of insulin. EGCg also induced GLUT4 translocation through a 5′-adenosine monophosphate-activated protein kinase (AMPK)-dependent pathway. 67 kDa laminin receptor, which is a target molecule of EGCg, was not involved in EGCg-induced glucose uptake in L6 cells. The oral administration of EGCg suppressed postprandial hyperglycaemia accompanied by GLUT4 translocation through both PI3K- and AMPK-dependent pathways, and promoted glycogen accumulation in skeletal muscle of ICR mice. EGCg promotes GLUT4 translocation through both PI3K- and AMPK-dependent pathways and glycogen accumulation in skeletal muscle. EGCg promotes GLUT4 translocation through both PI3K- and AMPK-dependent pathways and then promotes glycogen accumulation in soleus muscle.