Antihyperglycemic mechanism of M16209, an antidiabetic agent, in 3T3-L1 adipocytes.
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 M16209 (30 and 100 microM) was added to 3T3-L1 adipocytes and preincubated for 24 hours, the uptake of 2-deoxy-D-[3H]-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 M16209 did not increase the response to 600 ng/ml insulin. M16209 (100 microM) did not interfere with (125)I-insulin binding or with tyrosine phosphorylation of the insulin receptor beta-subunit and IRS-1. M16209 (100 microM) 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, M16209 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 beta-subunit, and tyrosine phosphorylation of IRS-1 were unaffected by M16209. However, translocation of GLUT4 from the intracellular pool to the plasma membrane was facilitated.
Murakami
N
N
Department of Pharmacology, Fuji Central Research Laboratory, Mochida Pharmaceutical Co., Ltd., Kita-ku, Tokyo, Japan.
Inoue
G
G
Okamoto
M
M
Yoshimasa
Y
Y
Kohno
S
S
Hayashi
T
T
Kato
K
K
Kuzuya
H
H
Nakao
K
K
D016475:3T3 Cells / Q000187:drug effects / Q000378:metabolism; D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism*; D000818:Animals; D001572:Benzofurans / Q000494:pharmacology*; D001692:Biological Transport / Q000187:drug effects; D016466:CHO Cells / Q000378:metabolism; D006224:Cricetinae; D005947:Glucose / Q000493:pharmacokinetics; D051272:Glucose Transporter Type 1; D051275:Glucose Transporter Type 4; D006827:Hydantoins / Q000494:pharmacology*; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism*; D055504:Insulin Receptor Substrate Proteins; D046911:Macromolecular Substances; D051379:Mice; D009004:Monosaccharide Transport Proteins / Q000187:drug effects / Q000378:metabolism; D009124:Muscle Proteins; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D011972:Receptor, Insulin / Q000378:metabolism; D015398:Signal Transduction; D014443:Tyrosine / Q000378:metabolism
D001572:Benzofurans; D051272:Glucose Transporter Type 1; D051275:Glucose Transporter Type 4; D006827:Hydantoins; D007004:Hypoglycemic Agents; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; C526295:Irs1 protein, mouse; D046911:Macromolecular Substances; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; D010750:Phosphoproteins; C495678:Slc2a1 protein, mouse; C495693:Slc2a4 protein, mouse; C068409:M 16209; D014443:Tyrosine; D011972:Receptor, Insulin; D005947:Glucose