THE LINOLEIC ACID DERIVATIVE DCP-LASHEDS LIGHT ON TYPE 1 DM THERAPY

The present study investigated the possibility for the linoleic acid derivative 8-[2-(2-pentyl-cyclopropylmethyl)-cyclopropyl]-octanoic acid (DCP-LA) as a novel drug of diabetes mellitus (DM).  DCP-LA had no effect on intracellulardistribution of the glucose transporter GLUT4 in differentiated 3T3-L1 adipocytes.  DCP-LA increased glucose uptake into adipocytes in a         bell-shaped concentration (0.01-100 M)-dependent manner, and the effect was not affected by the PKC inhibitor GF109203X.  In the oral glucose tolerance test (OGTT) using type 1 DM model mice treated with streptozotocin and type 2 DM model mice (C57BL/KsJ-leprdb/leprdb mice), intraperitoneal injection with insulin reduced serum glucose levels in a dose (0.2-1.2 x body weight U)-dependent manner.  Like insulin, oral administration with DCP-LA effectively reduced serum glucose levels in a dose (0.001-0.1 mg/kg)-dependent manner both in type 1 and type 2 DM model mice.  Taken together, these results indicate that DCP-LA is capable ofreducing serum glucose levels by the mechanism independent of that for insulin.  DCP-LA, therefore, could be developed as a novel DM drug, especially for type 1 DM.