Actions of novel antidiabetic agent englitazone in hyperglycemic hyperinsulinemic ob/ob mice.

摘要: The effects of CP 68722 (racemic englitazone) were examined in ob / mice, adipocytes and soleus muscles from 3T3-L1 adipocytes. Administration englitazone at 5–50 mg · kg−1 day−1 lowered plasma glucose insulin dose dependently without producing frank hypoglycemia either the diabetic or nondiabetic lean animals. glucoselowering effect mice preceded reduction hyperinsulinemia. On cessation drug, returned to untreated levels within 48 h, whereas rose slowly over 5 days. Englitazone (50 mg/kg) for 11 days (22.2 ± 1.4 14.0 1.9 mM), (7.57 0.67 1.64 0.60 nM), nonesterified fatty acids (1813 86 914 88 μM), glycerol (9.20 0.98 4.94 0.03 triglycerides (1.99 0.25 1.03 0.11 g/L), cholesterol (6.27 0.96 3.87 0.57 but no observed 3 h after a single dose. Basal insulin-stimulated lipogenesis enhanced treated with 50 mg/kg compared cells vehicle-treated controls. Treatment reversed defects glycolysis (from [3-3H]glucose) glycogenesis basal oxidation [1-14C]glucose) isolated muscles. (30 μM) stimulated 2- deoxy-D-glucose transport 0.37 0.65 0.06 1.53 nmol min−1 mg−1 protein 24 respectively. Thus, has 1) insulinomimetic insulin-enhancing actions vitro 2) glucose-, insulin-, triglyceride-, cholesterol-lowering properties an animal model non-insulin-dependent diabetes mellitus (NIDDM) which sulfonylureas have little effect. this new agent may beneficial including reduced risk patients NIDDM.