Protection against streptozotocin-induced diabetes by superoxide dismutase

Robbins, Melanie J.; Sharp, Robert A.; Slonim, Alfred E.; Burr, Ian M.

doi:10.1007/bf01228303

Cited by 92 publications

(48 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Their mechanisms of action are unknown, but since their actions are inhibited by superoxide dismutase (SOD) [4,5] or a chemical scavenger, such as 1,1-dimethylurea [6], they have been suggested to be related to the formation of free radicals. In fact, some reports strongly support the participation of free radicals in the action of alloxan [7,8].…”

Section: Introduction 2 Materials and Methodsmentioning

confidence: 99%

Enhancement by streptozotocin of O⁻₂ radical generation by the xanthine oxidase system of pancreatic β‐cells

et al. 1988

View full text Add to dashboard Cite

Spin-trapping techniques and electron spin resonance (ESR) spectroscopy were used to study the relationship between the effect of streptozotocin (STZ) on pancreatic B-cells and free radical formation by these cells. Results showed that STZ enhanced generation of the DMPO-OH radical adduct, which is a degradation product of the superoxide anion (0;) in the presence of cellular components, in a hypoxanthine-xanthine oxidase (XOD) system with a homogenate of b-cells. This enhancing effect was also observed in a system without cellular components; STZ increased the signal height due to the 0; radical in a concentration-dependent manner and caused a maximum of 150% enhancement at a concentration of 1.5 mM. Thus, STZ seemed to enhance the generation of the 0; radical in the XOD system, probably by some mechanism of its interaction with XOD. Pancreatic @ells exhibited a high XOD activity and a very low superoxide dismutase activity. Therefore, the present result supports the possibility that the cytotoxic effect of STZ is closely related to free radical generation in pancreatic l%ells.

show abstract

Section: Introduction 2 Materials and Methodsmentioning

confidence: 99%

Enhancement by streptozotocin of O⁻₂ radical generation by the xanthine oxidase system of pancreatic β‐cells

et al. 1988

View full text Add to dashboard Cite

show abstract

“…In vivo experiments show that transgenic mice with β cell-specific overexpression of Cu/Zn SOD are more resistant to alloxan-induced diabetes (11). Studies with rodents demonstrate that SOD administration can attenuate streptozotocin-induced (STZ-induced) hyperglycemia and diabetes (12)(13)(14). It was previously reported that antioxidant treatment exerts beneficial effects on β cell mass and insulin content in diabetic C57BL/KsJ-db/db mice (15).…”

Section: Introductionmentioning

confidence: 99%

Suppression of KATP channel activity protects murine pancreatic β cells against oxidative stress

et al. 2009

View full text Add to dashboard Cite

The enhanced oxidative stress associated with type 2 diabetes mellitus contributes to disease pathogenesis. We previously identified plasma membrane-associated ATP-sensitive K + (K ATP ) channels of pancreatic β cells as targets for oxidants. Here, we examined the effects of genetic and pharmacologic ablation of K ATP channels on loss of mouse β cell function and viability following oxidative stress. Using mice lacking the sulfonylurea receptor type 1 (Sur1) subunit of K ATP channels, we found that, compared with insulin secretion by WT islets, insulin secretion by Sur1 -/-islets was less susceptible to oxidative stress induced by the oxidant H 2 O 2 . This was likely, at least in part, a result of the reduced ability of H 2 O 2 to hyperpolarize plasma membrane potential and reduce cytosolic free Ca 2+ concentration ([Ca 2+ ] c ) in the Sur1 -/-β cells. Remarkably, Sur1 -/-β cells were less prone to apoptosis induced by H 2 O 2 or an NO donor than WT β cells, despite an enhanced basal rate of apoptosis. This protective effect was attributed to upregulation of the antioxidant enzymes SOD, glutathione peroxidase, and catalase. Upregulation of antioxidant enzymes and reduced sensitivity of Sur1 -/-cells to H 2 O 2 -induced apoptosis were mimicked by treatment with the sulfonylureas tolbutamide and gliclazide. Enzyme upregulation and protection against oxidant-induced apoptosis were abrogated by agents lowering [Ca 2+ ] c . Sur1 -/-mice were less susceptible than WT mice to streptozotocin-induced β cell destruction and subsequent hyperglycemia and death, which suggests that loss of K ATP channel activity may protect against streptozotocin-induced diabetes in vivo.

show abstract

“…Diabetes was assessed by IP glucose tolerance tests [6], following an overnight fast, 3 days after the injection of streptozotocin (50 mg/kg). Rats were maintained under light methoxyflurane anaesthesia throughout the glucose tolerance test.…”

Section: Methodsmentioning

confidence: 99%

“…A variety of chemical and enzymatic oxygen radical scavengers have now been used for protection against both alloxan and streptozotocin effects in vitro and in vivo. Intravenous injection of copper-zinc superoxide dismutase before streptozotocin prevents diabetes in rats [6,7]. Partial protection against alloxan was obtained in mice using a polyethylene glycol derivative of superoxide dismutase [8].…”

mentioning

confidence: 99%

Attenuation of streptozotocin diabetes with superoxide dismutase-like copper(II)(3,5-diisopropylsalicylate)2 in the rat

et al. 1983

View full text Add to dashboard Cite

Summary. Experimental diabetes can be produCed by agents with specific toxicity for pancreatic islet B cells. This effect has been reported to be modified both in vitro and in vivo by various radical scavengers including the enzyme superoxide dismutase. Copper(II)(3,5-diisopropylsalicylate)2 is lipophilic and possesses superoxide dismutase bioactivity. Prior administration of this compound to male rats appeared to attenuate the severity of streptozotocin-induced diabetes as assessed by glycosuria and glucose tolerance. Diisopropylsalicylate, which has no superoxide dismutase activity, did not alter the severity of streptozotocin-induced diabetes. Rats treated with the copper complex, with streptozotocin or with a combination of the two agents gained 50% less weight than untreated controls, or rats treated with diisopropylsalicylate. The attenuation of diabetes by the copper-complex may represent partial protection of the B cells against streptozotocin damage, although an extrapancreatic, toxic effect cannot be ruled out.

show abstract

Protection against streptozotocin-induced diabetes by superoxide dismutase

Cited by 92 publications

References 12 publications

Enhancement by streptozotocin of O⁻₂ radical generation by the xanthine oxidase system of pancreatic β‐cells

Enhancement by streptozotocin of O⁻₂ radical generation by the xanthine oxidase system of pancreatic β‐cells

Suppression of KATP channel activity protects murine pancreatic β cells against oxidative stress

Attenuation of streptozotocin diabetes with superoxide dismutase-like copper(II)(3,5-diisopropylsalicylate)2 in the rat

Contact Info

Product

Resources

About

Protection against streptozotocin-induced diabetes by superoxide dismutase

Cited by 92 publications

References 12 publications

Enhancement by streptozotocin of O−2 radical generation by the xanthine oxidase system of pancreatic β‐cells

Enhancement by streptozotocin of O−2 radical generation by the xanthine oxidase system of pancreatic β‐cells

Suppression of KATP channel activity protects murine pancreatic β cells against oxidative stress

Attenuation of streptozotocin diabetes with superoxide dismutase-like copper(II)(3,5-diisopropylsalicylate)2 in the rat

Contact Info

Product

Resources

About

Enhancement by streptozotocin of O⁻₂ radical generation by the xanthine oxidase system of pancreatic β‐cells

Enhancement by streptozotocin of O⁻₂ radical generation by the xanthine oxidase system of pancreatic β‐cells