Anti-diabetic effect and mechanism of compound A34 in diabetic mice

Abstract

In order to detemine the anti-diabetic effect and potential mechanism of a novel soluble epoxide hydrolas inhibitor (A34) on diabetic mice. Type 1 diabetes mellitus (T1DM) mice were induced by streptozotocin (50 mg/(kg·d) for 5 days, ip.)and the hypoglycemic effect of A34 were evaluated by water and food intake, non-fasting and fasting blood glucose, glucose tolerance and plasma insulin level in diabetic mice after water administration.The underlying mechanism was explored via measuring the expression level of sEH in islets, the morphological change of islets and the concerntration of cytokines INF-γ and IL-4 in plasma. Compared with diabetic model group, the water and food intake(p＜0.01, p＜0.05), blood glucose (p＜0.01), glucose tolerance (p＜0.01) and plasma insulin level (p＜0.05 ) were improved in A34 group. Additionally, A34 could protect pancreatic islet morphology, suppress sEH expression in islet (p＜0.01), reduce the ratio of INF-γ to IL-4 in plasma(p＜0.05 ). These results showed that A34 prevents hyperglycemia and β-cell dysfunction through regulating the dynamic balance of pro-inflammatory and anti-inflammatory cytokines in diabetic mice.

Keywords

• medicinal chemistry; soluble epoxide hydolase; type 1 diabetes mellitus; glucose tolerance; islet β cell; cytokines