Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:4.1.2.42 (DTA)
 1,693 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Microvascular complications are an important cause of morbidity in diabetic patients and can be detected in a significant number of patients at the time of diabetes diagnosis. However, little is known about the alterations in the microvasculature previous to the clinical manifestation of diabetes mellitus type 2. To obtain more insights into the early microvascular deterioration resulting from prediabetes, morphological and functional microvascular parameters were monitored using intravital fluorescence microscopy through a dorsal skin-fold chamber preparation in the uncoupling promotor-driven diphtheria toxin A chain (UCP1/DTA) mice. At the age of 12 weeks, the UCP1/DTA-mice were characterized by impaired glucose tolerance with concurrent unchanged fasting glucose, as well as dyslipidemia, hyperinsulinemia, hypertension and obesity. Prediabetic mice displayed combined hypertriglyceridemia and hypercholesterinemia. Associated with these prediabetic metabolic alterations, we demonstrate that microvascular density showed a dramatic decrease due to a reduction in perfused small vessels. A reduction in vascular density combined with unaltered blood flow in single vessels resulted in impaired tissue perfusion. Endothelial dysfunction with subsequently increased microvascular permeability and leukocyte-endothelium interactions were found. Our results of profound microvascular alterations at stages of normal fasting glucose underline the importance of early screening for prediabetes and associated microvascular complications.
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PMID:Early microvascular complications of prediabetes in mice with impaired glucose tolerance and dyslipidemia. 1936 64

Cardiac dysfunction in obesity is associated with mitochondrial dysfunction, oxidative stress and altered insulin sensitivity. Whether oxidative stress directly contributes to myocardial insulin resistance remains to be determined. This study tested the hypothesis that ROS scavenging will improve mitochondrial function and insulin sensitivity in the hearts of rodent models with varying degrees of insulin resistance and hyperglycemia. The catalytic antioxidant MnTBAP was administered to the uncoupling protein-diphtheria toxin A (UCP-DTA) mouse model of insulin resistance (IR) and obesity, at early and late time points in the evolution of IR, and to db/db mice with severe obesity and type-two diabetes. Mitochondrial function was measured in saponin-permeabilized cardiac fibers. Aconitase activity and hydrogen peroxide emission were measured in isolated mitochondria. Insulin-stimulated glucose oxidation, glycolysis and fatty acid oxidation rates were measured in isolated working hearts, and 2-deoxyglucose uptake was measured in isolated cardiomyocytes. Four weeks of MnTBAP attenuated glucose intolerance in 13-week-old UCP-DTA mice but was without effect in 24-week-old UCP-DTA mice and in db/db mice. Despite the absence of improvement in the systemic metabolic milieu, MnTBAP reversed cardiac mitochondrial oxidative stress and improved mitochondrial bioenergetics by increasing ATP generation and reducing mitochondrial uncoupling in all models. MnTBAP also improved myocardial insulin mediated glucose metabolism in 13 and 24-week-old UCP-DTA mice. Pharmacological ROS scavenging improves myocardial energy metabolism and insulin responsiveness in obesity and type 2 diabetes via direct effects that might be independent of changes in systemic metabolism.
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PMID:Antioxidant treatment normalizes mitochondrial energetics and myocardial insulin sensitivity independently of changes in systemic metabolic homeostasis in a mouse model of the metabolic syndrome. 2600 64