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)

Influenza is a viral infection of the respiratory tract spread by airborne transmission. Vaccination remains the best strategy for influenza prevention, and is especially recommended for high-risk groups, such as residents of nursing or residential homes, as well as those with diabetes, chronic renal failure, or chronic respiratory conditions. The clinician must realize the importance of active surveillance in addition to symptomatology interpretation and diagnostic testing to reliably and efficiently diagnose influenza. Active surveillance allows the clinician to monitor regional patterns of influenza movement to know when influenza is present in any given area. Surveillance data allows the practitioner to effectively time vaccination programs and implement prophylaxis protocols as indicated. An influenza management protocol ensuring the prompt recognition and management of influenza outbreaks should be devised and implemented for high-risk facilities. Managing clients with influenza requires prompt diagnosis and initiation of therapy, including use of antivirals available for the prevention or treatment of influenza. Because of the severity of morbidity and mortality caused by the influenza virus among older adults in particular, it is imperative that gerontological nurses have expert knowledge related to influenza. The clinician who participates in active influenza surveillance, promotes vaccination programs, implements influenza management protocols, and stays abreast of recent breakthroughs in the arena of influenza research--such as the development of neuraminidase inhibitors--will be able to contribute to diminishing the morbidity and mortality impact associated with influenza.
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PMID:Influenza. Past, present, and future. 1246

Experiments on white non-inbred male rats studied gastric sialoglycoprotein metabolism. It was found that rats with experimental (alloxan) diabetes exhibit enhanced catabolic processes in sialoglycoprotein metabolism characterized by elevated concentrations of free, oligobound sialic acids and sialidase activity in insignificantly elevated concentrations of protein-bound sialic acids.
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PMID:[Metabolism of sialoglycoproteins of the stomach of rats with experimental diabetes]. 1263 24

Plasma membrane-associated sialidase is a key enzyme for ganglioside hydrolysis, thereby playing crucial roles in regulation of cell surface functions. Here we demonstrate that mice overexpressing the human ortholog (NEU3) develop diabetic phenotype by 18-22 weeks associated with hyperinsulinemia, islet hyperplasia, and increased beta-cell mass. As compared with the wild type, insulin-stimulated phosphorylation of the insulin receptor (IR) and insulin receptor substrate I was significantly reduced, and activities of phosphatidylinositol 3-kinase and glycogen synthase were low in transgenic muscle. IR phosphorylation was already attenuated in the younger mice before manifestation of hyperglycemia. Transient transfection of NEU3 into 3T3-L1 adipocytes and L6 myocytes caused a significant decrease in IR signaling. In response to insulin, NEU3 was found to undergo tyrosine phosphorylation and subsequent association with the Grb2 protein, thus being activated and causing negative regulation of insulin signaling. In fact, accumulation of GM1 and GM2, the possible sialidase products in transgenic tissues, caused inhibition of IR phosphorylation in vitro, and blocking of association with Grb2 resulted in reversion of impaired insulin signaling in L6 cells. The data indicate that NEU3 indeed participates in the control of insulin signaling, probably via modulation of gangliosides and interaction with Grb2, and that the mice can serve as a valuable model for human insulin-resistant diabetes.
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PMID:Overexpression of plasma membrane-associated sialidase attenuates insulin signaling in transgenic mice. 1273 Feb 4

Influenza is a common illness, affecting many people every winter, with a considerable impact on mortality, hospital admissions, healthcare utilisation and sickness absence from work and school. Influenza management is currently focused on annual vaccinations for those in certain risk groups. Risk is determined by age and chronic illness, particularly diabetes, chronic respiratory and cardiac disease, and persons immunocompromised from disease or concomitant therapy. Amantadine (and in some countries, rimantadine is available but has not been widely used, because it is only effective against influenza A infections. The use of amantadines for treatment has been associated with the rapid emergence of resistant viruses capable of transmission, compromising its potential as a prophylactic, as well as a treatment. Side effects are well recognised and are a particular problem in the most vulnerable elderly populations, where dose restriction is necessary and prior knowledge of creatinine clearance desirable. The potential market for a new influenza treatment is large and the potential role of neuraminidase inhibitors in addressing this market has been covered in several review articles [1-4]. This review reports on the introduction of zanamivir (Relenza) to the market with particular reference to experience in the UK.
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PMID:Zanamivir in the treatment of influenza. 1274 2

Each year influenza epidemics cause a considerable burden of disease. Vaccination against influenza A and B viruses has been and remains the cornerstone of influenza prevention, but antiviral therapy can serve as an important adjunct to vaccination in controlling the impact of the disease. Two classes of drugs are currently licensed in a large number of countries for the treatment of influenza. The M2 ion channel blockers or amantadanes (amantadine and rimantadine) are specific inhibitors of influenza A virus replication, whereas the neuraminidase inhibitors (zanamivir and oseltamivir) are active against influenza A and B viruses. Readily transmissible drug-resistant viruses develop frequently during amantadane treatment but not during neuraminidase inhibitor treatment. In this review, efficacy and safety data from randomised controlled trials are evaluated to gain an understanding of what we can and cannot expect from antiviral treatment. All four drugs shorten the course of influenza disease by approximately 1 day and relieve symptoms to some extent, but there is still uncertainty as to whether antiviral therapy leads to a reduction of serious complications and hospitalisation. The results of cost-effectiveness analyses are very diverse, in part because of differences in methodology but also because there is no consensus on what probabilities to assign to the key risks and benefits that form the basis of these studies. Consensus statements by advisory bodies in England and Germany recommend neuraminidase inhibitors for the therapy of influenza in high-risk individuals such as people over 65 years or under 2 years, and individuals with chronic cardiovascular, pulmonary or renal disease, diabetes mellitus or immunosuppression. However, there is no agreement as to whether antiviral therapy can be generally recommended for otherwise healthy children and adults. The availability of safe and effective antiviral therapy options should be kept in mind by the practising clinician, while more specific recommendations and policy formulation will depend on additional efficacy data that include frequency of complications and hospitalisation as outcome measures.
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PMID:Antiviral therapy for influenza : a clinical and economic comparative review. 1534 96

Oligosaccharide processing enzymes such as glycosidases and glycosyltransferases are important classes of biocatalysts involved in synthesising specific oligosaccharide structures on proteins and lipids. These enzymes are known to be involved in a wide range of important biological processes, such as intestinal digestion, post-translational processing of glycoproteins, lysosomal catabolism of glycoconjugates and inter-cellular recognition events. Inhibition of these enzymes can disrupt biosynthesis of oligosaccharides, thus interfering in all of these processes. Hence, "glyco-enzyme" inhibitors might have enormous therapeutic potential in many diseases such as viral infection, cancer and diabetes. This very important prospect has led to increasing interest and demand for these compounds. Interference in oligosaccharide processing is the basis for the anti-influenza neuraminidase inhibitors that have recently been marketed and also for the potential use of glycosidase inhibitors against HIV, Gaucher's disease, hepatitis, and cancer. Since a rational design and synthesis of inhibitors are often extremely difficult due to the limited information regarding the structure of the active site, combinatorial approaches are particularly promising. This review will focus on synthetic efforts for the preparation of combinatorial libraries of glyco-enzyme inhibitors.
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PMID:Combinatorial approaches to iminosugars as glycosidase and glycosyltransferase inhibitors. 1701 77

Membrane microdomains rich in gangliosides are recognized as being critical for proper compartmentalization of insulin signaling. Plasma membrane-associated sialidase, NEU3, is a key enzyme for ganglioside hydrolysis. We previously reported that mice overexpressing NEU3 mainly in muscles developed severe insulin-resistant diabetes. To examine the possible contributions of NEU3 to in vivo insulin sensitivity and glucose tolerance, NEU3 was expressed by using adenoviral vectors in the livers of C57BL/6 mice on standard and high-fat diets, and insulin-resistant KKAy mice on standard diets. Hepatic NEU3 overexpression paradoxically improved glucose tolerance and insulin sensitivity in the C57BL/6 mice fed standard diets, and glucose tolerance in the C57BL/6 mice fed high-fat diets and in KKAy mice. Hepatic NEU3 overexpression increased hepatic glycogen deposition and triglyceride accumulation, and enhanced the hepatic peroxisome proliferator-activated receptor gamma and fetuin expression in the C57BL/6 mice on standard and high-fat diets, and in KKAy mice. Thin-layer chromatographic analysis demonstrated increased levels of GM1 and markedly reduced GM3 in the livers of mice with hepatic NEU3 overexpression (NEU3 mice). Basal and insulin-stimulated tyrosine phosphorylations of insulin receptor substrate 1 were significantly increased, but tyrosine phosphorylations of the insulin receptor and insulin receptor substrate 2 in the NEU3 liver were unchanged. Insulin-stimulated tyrosine phosphorylations of the insulin receptor were increased in adipose tissues of NEU3 mice. These results suggest that hepatic NEU3 overexpression improves insulin sensitivity and glucose tolerance through modification of ganglioside composition and peroxisome proliferator-activated receptor gamma signaling. Our findings also provide further evidence that NEU3 is an important regulator of insulin sensitivity and glucose tolerance.
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PMID:Increased hepatic expression of ganglioside-specific sialidase, NEU3, improves insulin sensitivity and glucose tolerance in mice. 1729 33

IgA1 was identified as the most prominent O-glycosylated protein of human serum. Desialylation by bacterial (Clostridium perfringens) neuraminidase rendered dot-blotted IgA1 recognizable by the naturally occurring serum antibody (anti-T) directed against Thomsen-Friedenreich antigen, Galbeta1-->3GalNAc-alpha-. On Western blot of serum O-glycosylated proteins anti-T recognized nearly all the bands including IgA1 as did the T antigen-specific animal lectin galectin-1 but only after their desialylation. Agglutination of desialylated human erythrocytes by anti-T was effectively inhibited by desialylated IgA1, but not by native IgA1 or other immunoglobulins. Desialylation of serum by neuraminidase led to significantly increased formation of immune complexes containing IgM, the major immunoglobulin type in anti-T on one hand and O-glycosylated proteins/IgA1 on the other. In further evidence for anti-T-desialylated IgA1 immune complex formation, purified anti-T added to desialylated, but not native serum led to formation of additional IgA-IgM immune complexes. Also neuraminidase treatment significantly reduced the titre of free (non-immune complexed) anti-T in serum, while selective removal of anti-T by affinity absorption resulted in considerable decrease in the amount of IgA1 that got converted to immune complexes following enzymatic desialylation of serum. Formation of immune complex between anti-T and neuraminidase-treated IgA1 in serum may be significant since many disease pathogens release neuraminidase and since IgA1 is a powerful ligand for tissue galectin-1 more so after desialylation. Diabetes also raises serum IgA and neuraminidase levels.
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PMID:IgA1 desialylated by microbial neuraminidase forms immune complex with naturally occurring anti-T antibody in human serum. 1804 97

The role of carbohydrate-related pathways in a wide range of clinically significant diseases has provided great impetus for researchers to characterise key proteins as targets for drug discovery. Carbohydrate-recognising proteins essential in the lifecycles of high health impact pathogens and diseases such as diabetes, cancer, autoimmunity, inflammation and in-born errors of metabolism continue to stimulate much interest in both structure elucidation and structure-based drug design. For example, advances in structure-based inhibitor design against the mycobacterial enzyme UDP-galactopyranose mutase offer new hope in next generation anti-tuberculosis chemotherapeutics. The appearance of H5N1 avian influenza virus has re-stimulated much research on influenza virus haemagglutinin and sialidase. These latest developments on influenza virus sialidase have provided new opportunity for the development of Group 1-specific anti-influenza drugs. The role of siglecs and galectins in a range of disease processes such as inflammation, apoptosis and cancer progression has also inspired significant structure-based inhibitor design research.
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PMID:Disease-associated carbohydrate-recognising proteins and structure-based inhibitor design. 1870 99

Recent advances in the sialidase biology have clarified the role of human sialidases (NEU 1 to NEU4) in the development of various disease states such as cancer, diabetes and arteriosclerosis. Isoform selective human sialidase inhibitors could be a therapeutic tool or molecular probes for the exploration of the specific functions of human sialidases. In the present study, de novo design based virtual screening was performed to find a new class of human sialidase inhibitors using the experimental crystal structure of NEU2 isoform. A few of nitro benzene and fluoro benzoic acid were identified and a series of 4-acetamido-5-acylamido-2-fluoro benzoic acids were synthesized and, the inhibitory activity of all these compounds against all human sialidase enzymes was evaluated. All these compounds were found to have a poor inhibitory activity and only NEU2 showed more sensitivity to this series of compounds as compared to other isoforms. Molecular docking was performed to gain insight regarding the binding mode of these inhibitors and thereby provided valuable information for our study on the design of selective human sialidase inhibitors further.
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PMID:Human sialidase inhibitors: design, synthesis, and biological evaluation of 4-acetamido-5-acylamido-2-fluoro benzoic acids. 1945 Sep 82


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