The Effect Of12-lipoxygenase On Insulin Resistance In Type2Diabetic Rat

Objective：To investigate the effect of12-lipoxygenase (12-LO) oninsulin resistance(IR) in type2diabetic rat.Methods：Podocytes were stimulated by12(S)-HETE (10-7mol/L)or/and insulin (10-6mol/L) for24hours. Rats fed high fat diet werereceived low dose streptozotocin (STZ,35mg/kg, intraperitoneal injection)to make type2diabetes and divided into2groups: low dose STZ (DNgroup),low dose STZ+12-LO inhibitor cinnamyl-3,4-dihydroxy-cynanocinnamate (CDC,8mg/kg)(CDC group). Rats fed regular chowwere as control group (Ctrl group). The rats received injection of CDC orvehicle subcutaneously in the hind legs．CDC or vehicle injection wasperformed three times a week. All rats were sacrificed after8weeks.Urine, blood, kidney and skeletal muscle from rat hind legs werecollected at the end of study respectively. The level of fasting seruminsulin, insulin sensitivity index and AMPK were designed as symbols forIR. ELISA and Western blot for related targets were performedrespectively.Results：12(S)-HETE and insulin increased angiotensinⅡ type1receptor (AT1R) levels in podocytes, respectively (P<0.01)．AT1R levelswere significantly increased by the combined stimulation of12(S)-HETEand insulin. Blood glucose (P<0.05), kidney/body weight (P<0.01) andurine protein (P<0.01) were increased in DN group compared with Ctrlgroup. However, urine protein (P<0.05)， Kidney/body weight(P<0.05)were decreased in CDC group compared with DN group. There was no change in blood glucose level between CDC group and DN group.Increment of fasting serum insulin (P<0.01) and decrement of p-AMPK(P<0.01)and insulin sensitivity index (P<0.01) were observed in DNgroup compared with Ctrl group. However, the abnormalities weresignificantly ameliorated after CDC treatment.Conclusion：12-LO affects the development of proteinuria in type2diabetic nephropathy via IR that relative to AT1R protein expression.