Amelioration of the β‐cell dysfunction in diabetic APA hamsters by antioxidants and AGE inhibitor treatments

Takatori, Atsushi; Ishii, Yoshiyuki; Itagaki, Shin-ichi; Kyuwa, Shigeru; Yoshikawa, Yasuhiro

doi:10.1002/dmrr.428

Cited by 27 publications

(18 citation statements)

References 43 publications

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“…52 In both of these studies, high levels of AGEs were shown to result in hyperglycemia. Given that prooxidants such as AGEs are toxic to pancreatic islets [53][54][55] and that anti-AGE agents and diets protect against islet and ␤-cell injury and dysfunction, 30,53 it is possible that AGER1 overexpression could protect against ␤-cell injury as a matter of course. Further studies are required to elucidate the mechanisms involved in these effects.…”

Section: Discussionmentioning

confidence: 99%

Advanced Glycation End Product Receptor-1 Transgenic Mice Are Resistant to Inflammation, Oxidative Stress, and Post-Injury Intimal Hyperplasia

Torreggiani¹,

Liu²,

Wu³

et al. 2009

The American Journal of Pathology

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The high levels of oxidative stress (OS) and inflammation associated with cardiovascular disease are linked to pro-oxidants such as advanced glycation end products (AGEs). AGEs interact with multiple receptors, including receptor 1 (AGER1), which promotes AGE removal and blocks OS and inflammation, and RAGE, which enhances inflammation. In this study, we evaluated metabolic and vascular changes in AGER1 transgenic mice (AGER1-tg) subjected to an atherogenic diet and arterial wire-injury. Both baseline and postatherogenic diet serum and tissue AGEs as well as plasma 8-isoprostane levels were lower in AGER1-tg mice than in wild-type mice. The levels of injected 125 I-AGE in tissues were decreased as well in AGER1-tg mice. After ingesting a high-fat diet, AGER1-tg mice had a normal glucose tolerance and only 7% were hyperglycemic, whereas 53% of wildtype mice had stable hyperglycemia. After wire-injury , intimal lesions in AGER1-tg mice were small , whereas wild-type mice had diffuse intimal hyperplasia , a high intima/media ratio , and inflammatory cell infiltrates. In addition , AGER1 staining , prominent in AGER1-tg mice , was attenuated in 30 to 40% of wild-type cells , although all cells were strongly positive for AGEs. Thus , AGER1 overexpression in mice reduces basal levels of AGEs and OS , enhances resistance to diet-induced hyperglycemia and OS , and protects against injury-induced arterial intimal hyperplasia and inflammation , providing protection against OS and inflammation induced by AGEs and high-fat diets in vivo. (Am J Pathol

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Section: Discussionmentioning

confidence: 99%

Advanced Glycation End Product Receptor-1 Transgenic Mice Are Resistant to Inflammation, Oxidative Stress, and Post-Injury Intimal Hyperplasia

Torreggiani¹,

Liu²,

Wu³

et al. 2009

The American Journal of Pathology

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“…A vitamin B-6-deficient diet increases plasma lipid peroxidation and decreases plasma vitamins E and C concentrations in rats (45). Experimental models have further shown that supplementation with vitamin B-6 suppresses the colonic concentrations of 8-OHdG induced by colonic carcinogen (46) and decreases plasma 8-OHdG and malonaldehyde in hyperglycemia-induced oxidative stress (37). Vitamin B-6 compounds can prevent the oxygen radical generation and lipid peroxidation caused by hydrogen peroxide in U937 monocytes as well (47).…”

Section: Discussionmentioning

confidence: 99%

“…Vitamin B-6 deficiency has been shown to cause degenerative changes in b cells in the islets of Langerhans and to decrease both pancreatic and circulating insulin (35,36). Likewise, pyridoxamine treatment of streptozotocin-induced diabetic hamsters improves glucose tolerance and restores b cell function (37). Moreover, supplementation with pyridoxine lowers blood glucose and decreases Hb A lc in diabetic patients (38,39).…”

Section: Discussionmentioning

confidence: 99%

Association of vitamin B-6 status with inflammation, oxidative stress, and chronic inflammatory conditions: the Boston Puerto Rican Health Study

Shen

Lai

Mattei

et al. 2010

The American Journal of Clinical Nutrition

125

129

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Background: Low vitamin B-6 status has been linked to an increased risk of cardiovascular diseases. The cardioprotective effects of vitamin B-6 independent of homocysteine suggest that additional mechanisms may be involved. Objective: Our objective was to examine the cross-sectional association of vitamin B-6 status with markers of inflammation and oxidative stress. Design: We measured plasma pyridoxal-5#-phosphate (PLP), Creactive protein (CRP), and an oxidative DNA damage marker, urinary 8-hydroxydeoxyguanosine (8-OHdG), in Puerto Rican adults who were living in Massachusetts (n = 1205, aged 45-75 y).Results: There was a strong dose-response relation of plasma PLP concentration with plasma CRP. Increasing quartiles of PLP were significantly associated with lower CRP concentrations (geometric means: 4.7, 3.6, 3.1, and 2.5 mg/L; P for trend , 0.0001) and with lower urinary 8-OHdG concentrations (geometric means: 124, 124, 117, and 108 ng/mg creatinine; P for trend: 0.025) after multivariate adjustment. These negative associations persisted after plasma homocysteine was controlled for. Plasma PLP concentrations were significantly correlated with plasma fasting glucose (r = 20.1, P = 0.0006), glycated hemoglobin (r = 20.08, P = 0.006), and homeostasis model assessment of b cell function (r = 0.082, P = 0.005). Metabolic syndrome, obesity, and diabetes were also significantly associated with low plasma PLP concentrations (P = 0.011, 0.0007, and 0.004, respectively). Conclusions: Low vitamin B-6 concentrations are associated with inflammation, higher oxidative stress, and metabolic conditions in older Puerto Rican adults. Our data suggest that vitamin B-6 may influence cardiovascular disease risk through mechanisms other than homocysteine and support the notion that nutritional status may influence the health disparities present in this population.Am J Clin Nutr 2010;91:337-42.

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“…Thus, mitochondrial dysfunction may contribute to the development of type 2 diabetes (4). Furthermore, diabetic hamsters treated with inhibitors of advanced glycation end products (AGEs) showed reduced oxidative stress and restored pancreatic ␤-cell function (7). However, the mechanism underlying the development of type 2 diabetes, how that mechanism relates to DNA damage, and how type 2 diabetes increases the risk of CVD are not well understood.…”

mentioning

confidence: 99%

PPARGC1A Variation Associated With DNA Damage, Diabetes, and Cardiovascular Diseases

et al. 2008

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OBJECTIVE-Individuals with type 2 diabetes exhibit higher DNA damage and increased risk of cardiovascular disease (CVD). However, mechanisms underlying the association between DNA damage and development of type 2 diabetes and CVD are not understood. We sought to link peroxisome proliferatoractivated receptor-␥ coactivator-1 ␣ (PPARGC1A), a master transcriptional regulator of mitochondrial oxidative phosphorylation and cellular energy metabolism, with DNA damage, type 2 diabetes, and CVD.RESEARCH DESIGN AND METHODS-We measured DNA damage as urinary 8-hydroxydeoxyguanosine (8-OHdG) concentration and examined the relationship between nine PPARGC1A genetic variants, DNA damage, type 2 diabetes, and self-reported CVD in 959 participants of the Boston Puerto Rican Health Study.RESULTS-With respect to urinary 8-OHdG, PPARGC1A variants showed significant association, and PPARGC1A haplotypes exhibited significant association after correction for multiple testing. Two independent PPARGC1A variants associated significantly with type 2 diabetes (odds ratios [ORs] 1.35 and 2.46; P ϭ 0.045 and Ͻ0.001). Carriers of minor alleles of two other PPARGC1A variants, both in strong linkage disequilibrium and associated with lower DNA damage, showed lower prevalence of CVD (ORs 0.53 and 0.65; P ϭ 0.030 and 0.175). Moreover, we found that physical activity correlated negatively with DNA damage.CONCLUSIONS-It is plausible that low physical activity combined with risk haplotyes contribute to the high prevalence of type 2 diabetes in this population. We propose that PPARGC1A influences development of type 2 diabetes and CVD via DNA damage. Increasing physical activity, which induces PPARGC1A expression, is a potential strategy to slow DNA damage, thereby decreasing the risk of CVD for individuals with type 2 diabetes.

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Amelioration of the β‐cell dysfunction in diabetic APA hamsters by antioxidants and AGE inhibitor treatments

Abstract: These data suggest that NAC and PM treatment of SZ-injected diabetic hamsters reduces oxidative stress and restores beta-cell function, but that AG treatment has little beneficial effect on the diabetic conditions of SZ-injected hamsters.

Cited by 27 publications

References 43 publications

Advanced Glycation End Product Receptor-1 Transgenic Mice Are Resistant to Inflammation, Oxidative Stress, and Post-Injury Intimal Hyperplasia

Advanced Glycation End Product Receptor-1 Transgenic Mice Are Resistant to Inflammation, Oxidative Stress, and Post-Injury Intimal Hyperplasia

Association of vitamin B-6 status with inflammation, oxidative stress, and chronic inflammatory conditions: the Boston Puerto Rican Health Study

PPARGC1A Variation Associated With DNA Damage, Diabetes, and Cardiovascular Diseases

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