ABSTRACT
Objective To investigate whether and how candesartan treatment can attenuate the deleterious influence of hyperglycemia in diabetic(db/db) mice.Methods Eight-week-old db/db mice were randomized into candesartan eilexetil (1 mg/kg) or placebo group via gavage for 6 weeks.Their age-matched nondiabetie littermates db/m mice were treated with placebo and acted as non-diabetic control group.After 6 weeks' treatment, intraperitoneal glucose tolerance test,immunohistochemical stainings of oxidative stress markers [8-(OH) dG,4- HNE,NADPH oxidase],insulin,CD31,Azan staining and electron microscopy observation of islet?-cells were perfermed.Results As compared with placebo group,the improvement in glucose tolerance and marked saving of islet?-cell mass with candesartan for 6 weeks were noted.There were also notably decreased staining intensity in oxidative stress markers,such as 8-(OH) dG,4-HNE,p22~(phox),gp91~(phox),as well as attenuated intra-islet Azan staining and enhanced endothelium marker CD31 staining in islet.Under electron microscope,candesartan-treated mice showed significantly increased granulation of insulin and ameliorated proliferations of endoplasmic reticulum and Golgi bodies.Furthermore,swelling of mitochondria was relieved to nearly normal.Conclusion After diabetic onset,candesartan treatment does not reverse the state of diabetes but may effectively improve glucose tolerance and protect?-cell function by attenuating oxidative stress,islet fibrosis,sparsity of blood supply and uhrastructure disruption,and thus delays the?-cell failure.