Antihyperglycemic mechanism of M16209, an antidiabetic agent, in 3T3-L1 adipocytes

Abstract We investigated the effect of M16209 (1-(3-bromobenzo[b]furan-2-ylsulfonyl)hydantoin) on glucose transport and the insulin signaling system in mouse-derived 3T3-L1 adipocytes. When M 16209 (30 and 100 μM) was added to 3T3-L1 adipocytes and preincubated for 24 hours, the uptake of 2-deoxy-D-[ 3 H]-glucose (2-DG) after insulin stimulation was enhanced. This effect was seen when preincubation with M16209 was performed in the presence of 6 and 20 ng ml insulin, but M 16209 did not increase the response to 600 ng ml insulin. M16209 (100 μM) did not interfere with 125 I-insulin binding or with tyrosine phosphorylation of the insulin receptor β-subunit and IRS-1. M16209 (100 μM) also had no effect on the level of glucose transporter (GLUT1 and GLUT4) protein, but it promoted the translocation of intracellular GLUT4 to the plasma membrane. In contrast, M 16209 had no effect on the translocation of GLUT1. In summary, M16209 enhanced 2-DG uptake by 3T3-L1 adipocytes. Insulin binding to its receptor, autophosphorylation of the insulin receptor β-subunit, and tyrosine phosphorylation of IRS-1 were unaffected by M 16209. However, translocation of GLUT4 from the intracellular pool to the plasma membrane was facilitated.