Vascular Dysfunction in Streptozotocin-Induced Experimental Diabetes Strictly Depends on Insulin Deficiency

Abstract

Objective: In previous studies we and others have shown that streptozotocin (STZ)-induced diabetes in rats is associated with vascular oxidative stress and dysfunction. In the present study, we sought to determine whether vascular dysfunction and oxidative stress strictly depend on insulin deficiency. Methods: The effects of insulin (2.5 U/day s.c., 2 weeks) therapy on vascular disorders in STZ-induced (60 mg/kg i.v., 8 weeks) diabetes mellitus (type I) were studied in Wistar rats. The contribution of NADPH oxidase to overall oxidative stress was investigated by in vivo (30 mg/kg/day s.c., 4 days) and in vitro treatment with apocynin. Results: Insulin therapy completely normalized blood glucose, body weight, vascular dysfunction and oxidative stress as well as increased cardiac reactive oxygen and nitrogen species formation in diabetic rats, although diabetes was already established for 6 weeks before insulin therapy was started for the last 2 weeks of the total treatment interval. Apocynin normalized cardiac NADPH oxidase activity, and L-NAME effects suggest a role for uncoupled endothelial nitric oxide synthase in diabetic vascular complications. Conclusions: Our findings indicate that STZ-induced diabetes is a model of insulin-dependent diabetes (type 1) and that cardiovascular complications are probably not associated with systemic toxic side effects of STZ.

Protective effects of Quercetin and chronic moderate exercise (training) against oxidative stress in the liver tissue of streptozotocin-induced diabetic rats

“…STZ-induced diabetic rats showed clinical signs that were specific of severe DM: weight loss, polyuria, polydipsia and polyphagia associated with hyperglycemia (28,34). In the present study sedentary diabetic rats (DS group) showed body weight loss and the training protocol restored this body weight reduction caused by the diabetic state.…”

Transplantation of bone marrow-derived endothelial progenitor cells attenuates myocardial interstitial fibrosis and cardiac dysfunction in streptozotocin-induced diabetic rats

“…Collectively, results in the current study confirmed previous findings demonstrating that cardiomyocytes apoptosis is associated with the progression of DCM, and that EPC implantation has the potential to prevent cardiomyocytes apoptosis in diabetic conditions. STZ treatment induces systemic generation of reactive oxygen species (ROS) by activating NADPH oxidase, thus leading to cardiac dysfunction (42). To further investigate the mechanisms by which EPCs exert their cardioprotective effects, the expression of NADPH oxidase subunit p67phox and mitochondrial ROS-eliminating enzyme MnSOD was examined.…”

Molecular Mechanisms of the Crosstalk Between Mitochondria and NADPH Oxidase Through Reactive Oxygen Species—Studies in White Blood Cells and in Animal Models

“…Endothelial superoxide formation by DHE staining in the presence and absence of the NOS inhibitor L-NAME (or D-NAME) at a concentration of 500 lM was used to assess the coupling state of eNOS (43,64). In healthy tissue, the NOS inhibitor blocks NO formation and thereby indirectly increases the DHE staining due to reduced break-down of superoxide by the reaction with NO.…”