Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Elevated levels of glycocojugates, commonly observed in the myocardium of diabetic animals and patients, are postulated to contribute to the myocardial dysfunction in diabetes. Previously, we reported that UDP-GlcNAc: Galbeta1-3GalNAcalphaRbeta1-6-N-acetylglucosaminyltransferas e (core 2 GlcNAc-T), a developmentally regulated enzyme of O-linked glycans biosynthesis pathway, is specifically increased in the heart of diabetic animals and is regulated by hyperglycemia and insulin. In this study, transgenic mice overexpressing core 2 GlcNAc-T with severe increase in cardiac core 2 GlcNAc-T activities were normal at birth but showed progressive and significant cardiac hypertrophy at 6 months of age. The heart of transgenic mice showed elevation of sialylated O-glycan and increases of c-fos gene expression and AP-1 activity, which are characteristics of cardiac stress. Furthermore, transfection of PC12 cells with core 2 GlcNAc-T also induced c-fos promoter activation, mitogen activated-protein kinase (MAPK) phosphorylation, Trk receptor glycosylation, and cell differentiation. These results suggested a novel role for core 2 GlcNAc-T in the development of diabetic cardiomyopathy and modulation of the MAP kinase pathway in the heart.-Koya, D., Dennis, J. W., Warren, C. E., Takahara, N., Schoen, F. J., Nishio, Y., Nakajima, T., Lipes, M. A., King, G. L. Overexpression of core 2 N-acetylglycosaminyltransferase enhances cytokine actions and induces hypertrophic myocardium in transgenic mice.
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PMID:Overexpression of core 2 N-acetylglycosaminyltransferase enhances cytokine actions and induces hypertrophic myocardium in transgenic mice. 1059 80

Enzyme catalase seems to be the main regulator of hydrogen peroxide metabolism. Hydrogen peroxide at high concentrations is a toxic agent, while at low concentrations it appears to modulate some physiological processes such as signaling in cell proliferation, apoptosis, carbohydrate metabolism, and platelet activation. Benign catalase gene mutations of 5' noncoding region (15) and intron 1 (4) have no effect on catalase activity and are not associated with disease. Catalase gene mutations have been detected in association with diabetes mellitus, hypertension, and vitiligo. Decreases in catalase activity in patients with tumors is more likely to be due to decreased enzyme synthesis rather than to catalase mutations.Acatalasemia, the inherited deficiency of catalase has been detected in 11 countries. Its clinical features might be oral gangrene, altered lipid, carbohydrate, homocysteine metabolism and the increased risk of diabetes mellitus. The Japanese, Swiss, and Hungarian types of acatalasemia display differences in biochemical and genetic aspects. However, there are only limited reports on the syndrome causing these mutations. These data show that acatalasemia may be a syndrome with clinical, biochemical, genetic characteristics rather than just a simple enzyme deficiency.
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PMID:Catalase enzyme mutations and their association with diseases. 1577 51

Mitochondrial reactive oxygen species (ROS) play an important role in diabetes complications, including diabetic nephropathy (DN). Plasma free fatty acids (FFAs) as well as glucose are increased in diabetes, and peroxisomes and mitochondria participate in FFA oxidation in an interconnected fashion. Therefore, we investigated whether deficiency of catalase, a major peroxisomal antioxidant, accelerates DN through peroxisomal dysfunction and abnormal renal FFA metabolism. Diabetes was induced by multiple injections of low-dose streptozotocin into catalase knock-out (CKO) and wild-type (WT) C57BL/6 mice. Murine mesangial cells (MMCs) transfected with catalase small interfering RNA followed by catalase overexpression were used to further elucidate the role of endogenous catalase. Despite equivalent hyperglycemia, parameters of DN, along with markers of oxidative stress, were more accelerated in diabetic CKO mice than in diabetic WT mice up to 10 weeks of diabetes. CKO mice and MMCs showed impaired peroxisomal/mitochondrial biogenesis and FFA oxidation. Catalase deficiency increased mitochondrial ROS and fibronectin expression in response to FFAs, which were effectively restored by catalase overexpression or N-acetylcysteine. These data provide unprecedented evidence that FFA-induced peroxisomal dysfunction exacerbates DN and that endogenous catalase plays an important role in protecting the kidney from diabetic stress through maintaining peroxisomal and mitochondrial fitness.
Diabetes 2012 Mar
PMID:Catalase deficiency accelerates diabetic renal injury through peroxisomal dysfunction. 2231 14

The enzyme catalase catalyzes the breakdown of hydrogen peroxide into oxygen and water. It is the main regulator of hydrogen peroxide metabolism. Hydrogen peroxide is a highly reactive small molecule formed as a natural byproducts of energy metabolism. Excessive concentrations may cause significant damages to protein, DNA, RNA and lipids. Low levels in muscle cells, facilitate insulin signaling. Acatalasemia is a result of the homozygous mutations in the catalase gene, has a worldwide distribution with 12 known mutations. Increased hydrogen peroxide, due to catalase deficiency, plays a role in the pathogenesis of several diseases such as diabetes mellitus. Diabetes mellitus is a disorder caused by multiple genetic and environmental factors. Examination of Hungarian diabetic and acatalasemic patients showed that an increased frequency of catalase gene mutations exists among diabetes patients. Inherited catalase deficiency may increase the risk of type 2 diabetes mellitus, especially for females. Early onset of type 2 diabetes occurs with inherited catalase deficiency. Low levels of SOD and glutathione peroxidase could contribute to complications caused by increased oxidative stress.
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PMID:Acatalasemia and diabetes mellitus. 2236 90

Hydrogen peroxide was - and is still - considered toxic for a wide range of living organisms. Oxidative stress occurs when there is an excess of pro-oxidants over antioxidants and it has been implicated in several diseases. Catalase is involved in hydrogen peroxide catabolism and is important in defense against oxidative stress. Acatalasemia means the inherited near-total deficiency of catalase activity, usually in reference to red cell catalase. Acatalasemia was thought at first to be an asymptotic disorder. In the absence of catalase, neither the Japanese, or Hungarian acatalasemics nor acatalasemic mice had significantly increased blood glutathione peroxidase activity. In animal models, catalase deficient tissues show much slower rates of removal of extracellular hydrogen peroxide. In catalase knock-out mice, a decreased hydrogen peroxide removing capacity and increased reactive oxygen species formation were reported. Hydrogen peroxide may cause methemoglobinemia in patients with catalase deficiency. During anesthesia for a Japanese acatalasemic patient the disinfection with hydrogen peroxide solution caused severe methemoglobinemia. Patients with inherited catalase deficiency, who are treated with uric acid oxidase (rasburicase) may experience very high concentrations of hydrogen peroxide and may suffer from methemoglobinemia and hemolysis. The high (18.5%) prevalence of diabetes mellitus in inherited catalase deficient individuals and the earlier (10 years) manifestation of the disease may be attributed to the oxidative damage of oxidant sensitive, insulin producing pancreatic beta-cells. Ninety-seven of 114 acatalasemics had diseases related to oxidative stress and aging. The oxidative stress due to catalase deficiency could contribute to the manifestation of diabetes while for the other diseases it may be one of the factors in their causations. In summary, inherited catalase deficiency is associated with clinical features, pathologic laboratory test results, age and oxidative stress related disorders. Rather than considering it a benign condition, it should be considered as a complicating condition for aging and oxidative stress.
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PMID:Inherited catalase deficiency: is it benign or a factor in various age related disorders? 2402 77