Free radicals and diabetes

Oberley, Larry W.

doi:10.1016/0891-5849(88)90036-6

Cited by 951 publications

(527 citation statements)

References 77 publications

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“…Iron is auto-oxidised to form highly reactive, lipid-soluble iron-oxygen complexes. These free radicals are powerful pro-oxidants, which can change membrane properties and result in tissue damage [22,23]. Oxidative stress can also lead to hyperglycaemia through disturbed glucose metabolism [24].…”

Section: Discussionmentioning

confidence: 99%

Elevated serum ferritin levels predict new-onset type 2 diabetes: results from the EPIC-Norfolk prospective study

et al. 2007

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Aims/hypothesis The aim of this study was to examine the association between baseline body iron stores and new-onset diabetes. Subjects and methods We studied the association between baseline serum ferritin concentration and type 2 diabetes in 360 clinically incident diabetes cases and 758 controls nested within the EPIC (European Prospective Investigation of Cancer)-Norfolk Cohort Study. Serum ferritin levels were categorised into five groups: sex-specific quartiles of the normal range of ferritin and a group with clinically raised ferritin below levels indicative of haemochromatosis. Results Baseline serum ferritin was higher among cases than control participants (geometric mean: men 96.6 vs 67.8 ng/ml, respectively, p<0.001; women 45.9 vs 34.8 ng/ ml, respectively, p=0.005). In analyses adjusted for known risk factors (age, BMI, sex, family history, physical activity, smoking habit) and dietary factors measured by 7-day food diary, the risk of diabetes was markedly elevated in participants with clinically raised ferritin compared with the lowest quartile (odds ratio [OR] 7.4, 95% CI 3.5-15.4). Further adjustment for potential confounding by inflammation (C-reactive protein, IL-6 and fibrinogen) had no material impact on the observed association, while adjustment for hepatic enzymes (alanine aminotransferase and γ glutamyl transferase) and adiponectin attenuated the magnitude of association, but it remained statistically significant (OR 3.2 [1.3-7.6]). Conclusions/interpretation Serum ferritin is an important and independent predictor of the development of diabetes. This finding may have important implications for understanding the aetiology of diabetes.

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Section: Discussionmentioning

confidence: 99%

Elevated serum ferritin levels predict new-onset type 2 diabetes: results from the EPIC-Norfolk prospective study

et al. 2007

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“…Reduced NO bioactivity may results from lower NO production [e.g. the inhibition of NOS activity, a deficit of Larginine as the natural NO donor [26]] or via enhanced NO degradation [increased oxidative stress and generation of oxygen free radicals [27,28]] contributed to the impairment of NO-dependent mechanisms. Light microscopy in our studies [10,29] correlates with quantitative image analysis showing significantly low capillary NOS activity within the myocardial tissue of both groups indicating diminished production of NO and the endothelial dysfunction.…”

Section: Discussionmentioning

confidence: 99%

Ultrastructure and histochemistry of rat myocardial capillary endothelial cells in response to diabetes and hypertension

et al. 2005

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Insufficient growth and rarefaction of capillaries, followed by endothelial dysfunction may represent one of the most critical mechanisms involved in heart damage. In this study we examined histochemical and ultrastructural changes in myocardial capillary endothelium in two models of heart failure streptozotocin-induced diabetes mellitus (STZ) and NOdeficient hypertension in male Wistar rats. Diabetes was induced by a single i.v. dose of STZ (45 mg/kg) and chronic 9-week stage was analysed. To induce NO-deficient hypertension, animals were treated with inhibitor of NO synthase Lnitroarginine methylester (L-NAME) (40 mg/kg) for 4 weeks. Left ventricular tissue was processed for enzyme catalytic histochemistry of capillary alkaline phosphatase (AlPh), dipeptidyl peptidase IV (DPP IV), and endothelial NO synthase/NADPH-diaphorase (NOS) and for ultrastructural analysis. In diabetic and hypertensive rats, lower/absent AlPh and DPP IV activities were found in focal micro-areas. NOS activity was significantly reduced and persisted only locally. Quantitative evaluation demonstrated reduction of reaction product intensity of AlPh, DPP and NOS by 49.50%, 74.36%, 20.05% in diabetic and 62.93%, 82.71%, 37.65% in hypertensive rats. Subcellular alterations of endothelial cells were found in heart of both groups suggesting injury of capillary function as well as compensatory processes. Endothelial injury was more significant in diabetic animals, in contrast the adaptation was more evident in hypertensive ones. Concluding: both STZ-induced diabetes-and NO-deficient hypertension-related cardiomyopathy were accompanied by similar features of structural remodelling of cardiac capillary network manifested as angiogenesis and angiopathy. The latter was however, predominant and may accelerate disappearance of capillary endothelium contributing to myocardial dysfunction.

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“…The major symptoms are thirst, hunger, emaciation, and weakness, eventually lead to coma. DM is associated with the increased production of free radicals or decreased activity of the antioxidant systems, which leads to development of oxidative stress [104,105]. The hyperglycemic condition induces increased free radical production via four different routes namely, 1) increased glycolysis, results in increased ratio between the rate of oxidation of G3P to 1, 3-DPG, following increased NADH/NAD ?…”

Section: Diabetes Mellitusmentioning

confidence: 99%

Free Radicals: Properties, Sources, Targets, and Their Implication in Various Diseases

2014

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Free radicals and other oxidants have gained importance in the field of biology due to their central role in various physiological conditions as well as their implication in a diverse range of diseases. The free radicals, both the reactive oxygen species (ROS) and reactive nitrogen species (RNS), are derived from both endogenous sources (mitochondria, peroxisomes, endoplasmic reticulum, phagocytic cells etc.) and exogenous sources (pollution, alcohol, tobacco smoke, heavy metals, transition metals,

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Free radicals and diabetes

Cited by 951 publications

References 77 publications

Elevated serum ferritin levels predict new-onset type 2 diabetes: results from the EPIC-Norfolk prospective study

Elevated serum ferritin levels predict new-onset type 2 diabetes: results from the EPIC-Norfolk prospective study

Ultrastructure and histochemistry of rat myocardial capillary endothelial cells in response to diabetes and hypertension

Free Radicals: Properties, Sources, Targets, and Their Implication in Various Diseases

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