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Cu superoxide dismutase (ZnCuSOD) on alloxan-induced diabetes in transgenic mice (TGHS-218)
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Session 1: Superoxide and Superoxide Dismutases EFFECTS OF ZINC STATUS AND INCREASED ZNKU SUPEROXIDE DISMUTASE (ZnCuSOD) ON ALLOXANINDUCED DIABETES IN TRANS$ENIC MICE (TGHS-21:) Junqiang Wanga, John. P. Phillips , and TTmy M. Bray Departments of aNutritional Sciences and Molecular Biology. University of Guelph, Guelph, Ontario, NlG 2Wl CANADA. Oxygen radicals are implicated in the pathogenesis of diabetes. Type I (insulin-dependent) diabetes can be produced experimentally in laboratory animals with alloxan, a drug that selectively destroys pancreatic islet p-cells. The mechanism of cytotoxicity of alloxan may be related to its metabolism which leads to production of oxygen radicals. Clinically, diabetic patients often have low plasma zinc and other antioxidant status. The importance of Zn in diabetes may be reflected in its requirement in insulin storage in islet p-cells, and as a component of ZnCuSOD. To examine the role of zinc status and ZnCuSOD in the protection against diabetes, transgenic mice, TGHS-218. a transgenic mouse line with increased ZnCuSOD levels in all somatic cells, and non-transgenic (NTG) mice were fed either a Zn deficient or a control diet for 2 weeks. A single dose of alloxan (50 rngkg-’ mouse, i.v.) was given at the end of two-week feeding regimens and the fasting blood glucose were measured daily for 9 days. Alloxan treatment caused 150% increase in the fasting blood glucose in NTG mice relative to the untreated mice. The fasting blood glucose level in TGHS-218 mice, however, was 50% lower than the NTG mice treated with It is suggested that elevated the same dose of alloxan. ZnCuSOD in mice have a protective effect against alloxaninduced diabetes. The onset diabetes was earlier and the concentration of fasting glucose was higher in mice fed two weeks of zinc deficient diet compared to mice fed control diet. Low zinc status resuted in increased susceptibility to alloxaninduced diabetes. Inject’on (i.p.) of a pharmacologic dose of zinc -1 (ZnSO4, 100 uMkg mouse) concurrently with alloxan, however, did not provide prophylaxis to alloxan-induced diabetes.
ESR SPIN-TRAPPING STUDY OF FREE RADICAL GENERATION IN ALLOXAN-INDUCED DIABETES IN RATS. Guaman Chena Edward Janzenb, and pmmy M. Braya Departments of ‘Nutritional Sciences and Clrnrcal Studies. University of Guelph, Guelph, Ontario, NlG 2Wl CANADA. The etiology of Type I diabetes is still unclear. Alloxan, a drug that selectively destroys pancreatic islet p-cells, is often used experimentally to produce insulin-dependent diabetes in laboratory animal. It has been suggested that free radicals are involved in the pathogenesis of alloxaninduced diabetes. The present study is designed to provide direct evidence of free radical generation in alloxan-induced diabetes. When alloxan was incubated with rat liver microsome, NADPH generating system and spin-trapping agent, phenyl-butyl-nitron (PBN), two types of free radicals were detected by ESR spin-trapping technique. One was hyperfine splitting 2.98 G which
is
other type of free radical gen rated in this syst hyperfine splitting constant of a identified as a lipid proxidation product. Addition of reducing agents such as glutathione (GSH) altered the concentration of free radicals gener ted. Injection of a single dose of alloxan (50 mgkg -P body weight, i.v.) caused a significant increase in the fasting blood glucose concentration in rats. Alloxan radical was also detected in vivo one hr after alloxan injection using PBN as the trapping agent. The result provided direct evidence that free radical is involved in the alloxan-induced diabetes.
1:25
Session 1: Superoxide and Superoxide Dismutases EFFECTS OF ZINC STATUS AND INCREASED ZNKU SUPEROXIDE DISMUTASE (ZnCuSOD) ON ALLOXANINDUCED DIABETES IN TRANS$ENIC MICE (TGHS-21:) Junqiang Wanga, John. P. Phillips , and TTmy M. Bray Departments of aNutritional Sciences and Molecular Biology. University of Guelph, Guelph, Ontario, NlG 2Wl CANADA. Oxygen radicals are implicated in the pathogenesis of diabetes. Type I (insulin-dependent) diabetes can be produced experimentally in laboratory animals with alloxan, a drug that selectively destroys pancreatic islet p-cells. The mechanism of cytotoxicity of alloxan may be related to its metabolism which leads to production of oxygen radicals. Clinically, diabetic patients often have low plasma zinc and other antioxidant status. The importance of Zn in diabetes may be reflected in its requirement in insulin storage in islet p-cells, and as a component of ZnCuSOD. To examine the role of zinc status and ZnCuSOD in the protection against diabetes, transgenic mice, TGHS-218. a transgenic mouse line with increased ZnCuSOD levels in all somatic cells, and non-transgenic (NTG) mice were fed either a Zn deficient or a control diet for 2 weeks. A single dose of alloxan (50 rngkg-’ mouse, i.v.) was given at the end of two-week feeding regimens and the fasting blood glucose were measured daily for 9 days. Alloxan treatment caused 150% increase in the fasting blood glucose in NTG mice relative to the untreated mice. The fasting blood glucose level in TGHS-218 mice, however, was 50% lower than the NTG mice treated with It is suggested that elevated the same dose of alloxan. ZnCuSOD in mice have a protective effect against alloxaninduced diabetes. The onset diabetes was earlier and the concentration of fasting glucose was higher in mice fed two weeks of zinc deficient diet compared to mice fed control diet. Low zinc status resuted in increased susceptibility to alloxaninduced diabetes. Inject’on (i.p.) of a pharmacologic dose of zinc -1 (ZnSO4, 100 uMkg mouse) concurrently with alloxan, however, did not provide prophylaxis to alloxan-induced diabetes.
ESR SPIN-TRAPPING STUDY OF FREE RADICAL GENERATION IN ALLOXAN-INDUCED DIABETES IN RATS. Guaman Chena Edward Janzenb, and pmmy M. Braya Departments of ‘Nutritional Sciences and Clrnrcal Studies. University of Guelph, Guelph, Ontario, NlG 2Wl CANADA. The etiology of Type I diabetes is still unclear. Alloxan, a drug that selectively destroys pancreatic islet p-cells, is often used experimentally to produce insulin-dependent diabetes in laboratory animal. It has been suggested that free radicals are involved in the pathogenesis of alloxaninduced diabetes. The present study is designed to provide direct evidence of free radical generation in alloxan-induced diabetes. When alloxan was incubated with rat liver microsome, NADPH generating system and spin-trapping agent, phenyl-butyl-nitron (PBN), two types of free radicals were detected by ESR spin-trapping technique. One was hyperfine splitting 2.98 G which
is
other type of free radical gen rated in this syst hyperfine splitting constant of a identified as a lipid proxidation product. Addition of reducing agents such as glutathione (GSH) altered the concentration of free radicals gener ted. Injection of a single dose of alloxan (50 mgkg -P body weight, i.v.) caused a significant increase in the fasting blood glucose concentration in rats. Alloxan radical was also detected in vivo one hr after alloxan injection using PBN as the trapping agent. The result provided direct evidence that free radical is involved in the alloxan-induced diabetes.