Sennidin stimulates glucose incorporation in rat adipocytes.
A novel small molecule compound which exerts insulin mimetic is desirable. Dozens of natural products that have quinone, naphthoquinone, or anthraquinone structure, were tested by a glucose incorporation assay. We found that sennidin A, anthraquinone derivative, stimulated glucose incorporation to near level of maximal insulin-stimulated and sennidin B, a stereoisomer of sennidin A, also stimulated, but the activity of sennidin B was lower than sennidin A. Sennidin A-stimulated glucose incorporation was completely inhibited by wortmannin. Sennidin A did not induce tyrosine phosphorylation of insulin receptor (IR) and insulin receptor substrate-1 (IRS-1), but induced phosphorylation of Akt and glucose transporter 4 (GLUT4) translocation. Our results suggest that in rat adipocytes, sennidin A stimulates glucose incorporation in the phosphatidylinositol 3-kinase (PI3K)- and Akt-dependent, but in the IR/IRS1-independent manner.
Abe
Daigo
D
National Agricultural Research Center for Western Region, 1-3-1 Senyu-cho, Zentsuji, Kagawa 765-8508, Japan.
Saito
Takeshi
T
Sekiya
Keizo
K
D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism*; D000818:Animals; D000873:Anthracenes / Q000737:chemistry / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism*; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D055504:Insulin Receptor Substrate Proteins; D008297:Male; D019869:Phosphatidylinositol 3-Kinases / Q000187:drug effects; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D021381:Protein Transport / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D011972:Receptor, Insulin / Q000378:metabolism; D014443:Tyrosine
D000873:Anthracenes; D051275:Glucose Transporter Type 4; D055504:Insulin Receptor Substrate Proteins; C526296:Irs1 protein, rat; D010750:Phosphoproteins; D014443:Tyrosine; C013946:dihydroxydianthrone; D019869:Phosphatidylinositol 3-Kinases; D011972:Receptor, Insulin; D051057:Proto-Oncogene Proteins c-akt; D005947:Glucose