Antidiabetic and insulin-sensitizing effects of neoglitazone in different animal models of type 2 diabetes / 中国新药与临床杂志

ABSTRACT

AIM To assess antidiabetic and insulin sensitizing effect of a novel thiazolidinedione,neoglitazone, in different animal models of type 2 diabetes. METHODS Neoglitazone combined with low-dose insulin(0.2U·d-1 per mouse,sc)were given in streptozotiocin (STZ)-induced diabetic mice for 7 d to inspect its insulin-sensitive improvement. The antidiabetic effect of chronic oral treatment (8 wk) with neoglitazone on spontaneous diabetes mice (DB/DB mice) was examined. The levels of blood glucose were measured by a One-Touch blood glucose meter and pathology of heart, kidney, and pancreas tissues were observed under a light microscope. The hyperinsulinaemic-euglycaemic clamp technique was applied to measure the increase of glucose infusion rate (GIR) of neoglitazone on the immune insulin-resistant rats induced by Bacillus Calmette-Guerin therapy decreased ( 14±s4)%, (55±24)%,and (28±7)% of blood glucose levels compared with CMC-Na+insulin group, respectively (P < 0.01) . In DB/DB mice, neoglitazone showed better reduction in blood glucose levels than those of model animals (P < 0.01) , and pathological studies indicated that neoglitazone attenuated the diabetic kidney and pancreas lesions. During a hyperinsulinaemic-euglycaemic clamp,neoglitaxone(10,30,and 100mg·kg-1·d-1,ig for 2 wk )-treated groups required significantly higher GIR to maintain basal glucose concentrations than model group (P < 0.01 ). CONCLUSION Neoglitazone could directly enhance insulin sensitivity and ameliorate insulin resistance in different diabetic animal models.