Establishment of new highly insulin-sensitive cell lines and screening of compounds to facilitate glucose consumption.
To obtain compounds that promote glucose uptake in muscle cells, the novel cell lines A31-IS derived from Balb/c 3T3 A31 and C2C12-IS from mouse myoblast C2C12 were established. In both cell lines, glucose consumption was induced by insulin and suppressed by the addition of Akt-activating kinase inhibitor. The A31-IS cells highly express the insulin receptor beta chains, Glut4, and uncoupling protein-3, as compared to the parent Balb/c 3T3 A31 cells, and C2C12-IS cells highly express the insulin receptor beta chain as compared to its parent cell line. Using A31-IS cells, we screened our library compounds and obtained three compounds, DF-4394, DF-4451, and DG-5451. These compounds dose-dependently promoted glucose consumption in A31-IS cells and facilitated [3H]-2-deoxyglucose uptake in differentiated C2C12-IS cells. The compounds that we obtained from the library screening will be good candidates for improving insulin resistance in muscle cells.
Hayata
Kenji
K
R&D Division, Exploratory Research Laboratories II, Daiichi-Sankyo Co., Ltd., Tokyo, Japan. hayata.kenji.v6@daiichisankyo.co.jp
Sakano
Katsuichi
K
Nishinaka
Shigeyuki
S
D000818:Animals; D041702:BALB 3T3 Cells; D002469:Cell Separation; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000378:metabolism*; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D007473:Ion Channels / Q000378:metabolism; D051379:Mice; D024101:Mitochondrial Proteins / Q000378:metabolism; D032342:Muscle Cells / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011972:Receptor, Insulin / Q000378:metabolism; D054852:Small Molecule Libraries; D000071247:Uncoupling Protein 3
D051275:Glucose Transporter Type 4; D007004:Hypoglycemic Agents; D007328:Insulin; D007473:Ion Channels; D024101:Mitochondrial Proteins; D047428:Protein Kinase Inhibitors; C495693:Slc2a4 protein, mouse; D054852:Small Molecule Libraries; C000604393:Ucp3 protein, mouse; D000071247:Uncoupling Protein 3; D011972:Receptor, Insulin; D051057:Proto-Oncogene Proteins c-akt; D005947:Glucose