Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Maternal malnutrition is known to impair fetal growth and predispose to the development of hypertension and type 2 diabetes. Recently, studies have demonstrated that intrauterine malnutrition is followed later in male offspring by oxidative stress characterized by increased superoxide generation due to activation of NADPH oxidase and reduced antioxidant defenses. However, few studies have investigated the mechanisms involved in endothelial dysfunction in female offspring. We evaluated the effects of the exogenous application of superoxide scavengers on the endothelium-dependent vasorelaxation in the mesenteric microvessels of female offspring. In addition, we examined indicative parameters of oxidative stress by measuring superoxide anion concentration and the activity of superoxide dismutase (SOD) as a marker of antioxidant defenses. Pregnant female Wistar rats were fed either a normal diet or 50% of this, throughout gestation. Intrauterine malnutrition induced hypertension and increased superoxide production without affecting SOD activity. Topical application of MnTMPyP (SOD mimetic) and apocynin (NADPH oxidase inhibitor) significantly improved the altered arteriolar responses to acetylcholine and bradykinin. In addition, incubation with apocynin reduced superoxide generation in these female offspring. The data suggest that after exposure to intrauterine malnutrition, female offspring present an increased superoxide production that is, at least in part, responsible for an endothelial dysfunction observed in these animals. These effects may be mediated via modulation of enzyme systems that generate superoxide.
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PMID:Long-term effects of intrauterine malnutrition on vascular function in female offspring: implications of oxidative stress. 1715 80

Intrauterine malnutrition predisposes the offspring towards the development of type 2 diabetes and cardiovascular disease. To explain this association, the Developmental Origins of Health and Disease hypothesis was introduced, meaning that subtle environmental changes during embryonic and foetal development can influence post-natal physiological functions. Different mechanisms, including epigenetics, are thought to be involved in this foetal programming, but the link between epigenetics and disease is missing. There is increasing evidence that ectopic lipid accumulation and/or lipotoxicity is induced by foetal programming. The aim of this review is to provide insights into the mechanisms underlying lipotoxicity through programming, which contributes to the increase in hepatic and cardiac metabolic risk.
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PMID:Lipotoxicity and the role of maternal nutrition. 2411 80