Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In order to obtain a quantitative estimate of the capacity of the pancreatic islets for provision of cytoplasmic acetyl-coenzyme A and for the turnover of nicotinamide adenine dinucleotide phosphate and its reduced form (NADP+/NADPH), the following enzymes were assayed in islets taken from New Zealand Obese mice: adenosine triphosphate citrate lyase (EC 4.1.3.8), malate dehydrogenase (decarboxylating) (NADP+) (EC 1.1.1.40), glutathione reductase (EC 1.6.4.2) and isocitrate dehydrogenase (NADP+) (EC 1.1.1.42). In addition, the activity of isocitrate dehydrogenase (NAD+) (EC 1.1.1.41) was determined. For comparative purposes the activities in exocrine pancreas, liver, heart muscle, kidney cortex and skeletal muscle were also determined. Specimens of pancreatic islets and the other tissues were microdissected from freeze-dried sections. In comparison with the other tissues, adenosine triphosphate citrate lyase was particularly active in the islets. The NADP+/NAPH-converting enzymes had activities, which suggested a rapid turnover of the islet NADP+/NADPH pool.
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PMID:Nicotinamide adenine dinucleotide phosphate-converting enzymes and adenosine triphosphate citrate lyase in some tissues and organs of New Zealand obese mice with special reference to the enzyme pattern of the pancreatic islets. 24 Aug 82

1. In biopsy samples of the lateral part of m. quadriceps femoris of 49 obese and 14 lean persons the activities of the following enzymes were investigated: triosephosphate dehydrogenase (TPDH), glycerolphosphate: nad dehydrogenase (GPDH), lactate dehydrogenase (LDH), hexokinase (HK), malate: NAD dehydrogenase (MDH), citrate synthase (CS) and hydroxyacyl-CoA dehydrogenase (HOADH). 2. The muscles of obese had an increased activity ratio of TPDH to CS and to HK, respectively, caused in muscles of female obese subjects by an increase of TPDH activity, in those of obese men rather by a decrease of CS and HK activities. 3. Cluster analysis brough to light the existence of three major groups. Group 1 (low activity-low LDH group), consisting of muscles of female obese subjects only, exhibited low activities of all enzymes investigated, that of LDH being so low as to possibly induce a serious deficiency of anerobic metabolism under working conditions. Group 2 (medium enzyme activity group) was characterized by medium enzyme activities, similar to that of lean controls (included in this group). This consisted of subjects of both sex. Group 3 (high enzyme activity group) consisted of obese of both sex. It was distinguished by high enzyme activities, especially of LDH. It is suggested that the groups of similar enzyme activity patterns might reflect different stages, types and/or genesis of obesity.
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PMID:Metabolic changes in the quadriceps femoris muscle of obese people. Enzyme activity patterns of energy-supplying metabolism. 123 24

The conversion of xanthine dehydrogenase to xanthine oxidase that produces oxygen radicals has been implicated in the ischemic injury to the myocardium and to the kidney. Xanthine dehydrogenase uses NAD as the electron acceptor to catalyze a reaction which does not produce any oxygen free radicals and may depress the conversion of xanthine dehydrogenase to xanthine oxidase. Nicotinamide is the preferred precursor for NAD. This study was conducted to examine the effect of an 18% casein diet supplemented with 0.5% nicotinamide on the activity of oxidoreductase and its two enzyme forms, xanthine dehydrogenase and xanthine oxidase, in kidney, heart and liver of female obese Zucker rats that spontaneously develop glomerulosclerosis, cardiomegaly and fatty liver. Lean litter mates were used as controls. Nicotinamide supplementation had no effect on the activities of these enzyme forms in the liver of either obese rats or lean rats. Obese rats fed the nicotinamide supplemented diet had higher activities of these enzyme forms in kidneys and hearts than unsupplemented diet fed obese rats, but this difference was not observed in lean rats. In unsupplemented rats, xanthine oxidase activity in the kidney was greater in lean rats than obese rats. Thus, the abnormalities observed in obese rats are unlikely attributable to the xanthine oxidase-mediated oxidant stress.
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PMID:Dietary nicotinamide supplementation increases xanthine oxidoreductase activity in the kidney and heart but not liver of obese Zucker rats. 761 99

Noise exposure has been associated with increased catecholamine production and blood pressure elevation in laboratory studies and in human volunteers. Epidemiologic studies have given conflicting results. In order to determine whether noise-induced hearing loss predicts a rise in blood pressure, we reviewed occupational medicine records in an occupational health center serving three companies where noise exposure is commonly found. Height, weight, blood pressure, and screening audiometry are obtained as part of routine occupational health screening, and the results of the screening visit are abstracted from written clinical records. The results of pure tone screening audiometry are reported in nonstandardized fashion (Normal, WNL, NAD, for example, for normal). We reviewed records from 1990 and 1991 inclusive. One investigator, blind to blood pressure status, assigned each record to "no hearing loss," "not codable," or "hearing loss assumed to be due to noise" on the basis of the written audiometry report. Hearing loss due to causes other than noise was considered not codable. No attempt was made to quantify severity of hearing loss. Two hundred and sixteen charts were excluded as "not codable," 1,535 were classified as having no hearing loss, and 610 had some degree of hearing loss, most probably due to noise exposure. To adjust for confounding covariates, multiple regression analysis was used and indicated that hearing status improves the regression model for predicting diastolic blood pressure (p = 0.04), following age, nationality, body mass index (BMI), and month of testing, although the effect is small. Stratification by age and BMI revealed increased diastolic pressure in the group with hearing loss under age 45, regardless of obesity.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Noise-induced hearing loss, nationality, and blood pressure. 858 24

Two isoforms of the enzyme 11beta-hydroxysteroid dehydrogenase (11beta-HSD) interconvert the active glucocorticoid, cortisol, and inactive cortisone. 11beta-HSD1 is believed to act in vivo predominantly as an oxo-reductase using NADP(H) as a cofactor to generate cortisol. In contrast, 11beta-HSD2 acts exclusively as an NAD-dependent dehydrogenase inactivating cortisol to cortisone, thereby protecting the mineralocorticoid receptor from occupation by cortisol. In peripheral tissues, both enzymes serve to control the availability of cortisol to bind to the corticosteroid receptors. Defective expression of 11beta-HSD2 is implicated in patients with hypertension and intra-uterine growth retardation, while 11beta-HSD1 appears to be intricately involved in the conditions of apparent cortisone reductase deficiency, insulin resistance and visceral obesity. The ability of peripheral tissues to regulate corticosteroid concentrations through 11beta-HSD isozymes is established as an important mechanism in the pathogenesis of diverse human diseases. Modulation of enzyme activity may offer a novel therapeutic approach to treating human disease while circumventing the consequences of systemic glucocorticoid excess or deficiency.
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PMID:Cortisol metabolism and the role of 11beta-hydroxysteroid dehydrogenase. 1146 11

Insulin resistance is a component of type 2 diabetes and often precedes pancreatic beta-cell failure. Contributing factors include obesity and a central pattern of fat accumulation with a strong genetic component. The adipocyte secreted hormone resistin has been proposed as a link between the adipocyte and insulin resistance by inhibition of insulin-stimulated glucose uptake and/or blocking adipocyte differentiation. Here we report that the G/G genotype of a single nucleotide polymorphism (SNP) in the promoter of the human resistin gene, -180C>G, had significantly increased basal promoter activity in adipocytes. These data were recapitulated in vivo, where G/G homozygotes had significantly higher resistin mRNA levels in human abdominal subcutaneous fat. A significant interaction was also found between the -180C>G SNP, a marker of oxidative stress (NAD[P]H quinone oxidoreductase mRNA) and homeostasis model assessment of insulin resistance. In addition, resistin mRNA was positively and independently correlated with insulin resistance and hepatic fat as measured by liver X-ray attenuation. These data implicate resistin in the pathophysiology of the human insulin resistance syndrome, an effect mediated by the -180C>G promoter SNP and potentially cellular oxidative stress.
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PMID:A promoter genotype and oxidative stress potentially link resistin to human insulin resistance. 1282 23

The first part of this report on the Australian Health and Medical Research Congress, held November 25-29, 2002, in Melbourne, Australia, considers some of the symposia and three plenary lectures: Neurosteroids: Nature's Valium, G-Protein-Coupled Receptors and the Mike Rand Memorial Lecture. In the new era in relaxin research symposium, we learned that relaxin is a general antifibrotic agent rather than just a hormone of pregnancy. The drugs discussed in the drug discovery symposium included drugs from natural products, allosteric modulators, antibodies to cytokines and AM-336, an N-type Ca(2+) channel blocker. In the matrix proteases symposium, we learned of the importance of these enzymes in bone, endometrial remodeling and cardiovascular disease. The emphasis of the cytokine antagonist symposium was the involvement of cytokines in rheumatoid arthritis and how these effects could be inhibited with cytokine antagonists. The second part of this report is on the cardiovascular components of the meeting. One of the major strengths of Australian research is the cardiovascular area. Thus, it was not surprising that there were three major symposia with a cardiovascular theme this congress. Although the clinical trials of the NHE1 inhibitors in ischemia and reperfusion have been disappointing to date, evidence was presented in the sodium-hydrogen exchanger symposium that these agents might be beneficial in hypertrophy and heart failure. The discussion in the vessel wall biology in diabetes symposium ranged from molecular aspects to clinical trials. In this, and the NAD(P)H oxidases symposium, many new potential drug targets were discussed. The plenary lecture of the High Blood Pressure Research Council concerned the pathophysiology and management of obesity hypertension, and included a discussion of the drugs for weight reduction.
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PMID:Health and medical research down under in 2002. 1294 54

Two isoforms of 11beta-hydroxysteroid dehydrogenase (11beta-HSD) interconvert the active glucocorticoid, cortisol, and inactive cortisone. 11beta-HSD1 acts predominantly as an oxo-reductase in vivo using NADP(H) as a cofactor to generate cortisol. In contrast, 11beta-HSD2 is a NAD-dependent dehydrogenase inactivating cortisol to cortisone, thereby protecting the mineralocorticoid receptor from occupation by cortisol. In peripheral tIssues, both enzymes serve to control the availability of cortisol to bind to corticosteroid receptors. 11beta-HSD2 protects the mineralocorticoid receptor from cortisol excess; mutations in the HSD11B2 gene explain an inherited form of hypertension, the syndrome of 'apparent mineralocorticoid excess', in which 'Cushing's disease of the kidney' results in cortisol-mediated mineralocorticoid excess. Inhibition of 11beta-HSD2 explains the mineralocorticoid excess state seen following liquorice ingestion and more subtle defects in enzyme expression might be involved in the pathogenesis of 'essential' hypertension. 11beta-HSD1 by generating cortisol in an autocrine fashion facilitates glucocorticoid receptor-mediated action in key peripheral tIssues including liver, adipose tissue, bone and the eye. 'Cushing's disease of the omentum' has been proposed as an underlying mechanism in the pathogenesis of central obesity and raises the exciting possibility of selective 11beta-HSD1 inhibition as a novel therapy for patients with the metabolic syndrome. 'Pre-receptor' metabolism of cortisol via 11beta-HSD isozymes is an important facet of corticosteroid hormone action. Aberrant expression of these isozymes is involved in the pathogenesis of diverse human diseases including hypertension, insulin resistance and obesity. Modulation of enzyme activity may offer a future therapeutic approach to treating these diseases whilst circumventing the endocrine consequences of glucocorticoid excess or deficiency.
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PMID:Tissue-specific Cushing's syndrome, 11beta-hydroxysteroid dehydrogenases and the redefinition of corticosteroid hormone action. 1294 16

Human CD38 is a protein which catalyzes the synthesis of nicotinic acid adenine dinucleotide (NAADP+) and the conversion of NAD+ to cADPR. Both cADPR and NAADP+ are powerful intracellular Ca2+ ([Ca2+]i) mobilizers in different cell types. Recently, the presence of CD38 autoantibodies has been found in a significant number (9-15%) of patients with Type 2 or long-standing Type 1 diabetes. These autoantibodies are biologically active, the majority of them (-60%) displaying agonistic properties, i.e., [Ca2+]i mobilization in lymphocytic cell lines and in pancreatic islets. In cultured rat pancreatic islets, the human autoantibodies inhibit glucose-induced insulin release, whereas, in human pancreatic islets CD38 autoantibodies stimulate glucose-mediated insulin secretion. The clinical phenotype of anti-CD38-positive Type 2 diabetes differs from the LADA (latent autoimmune diabetes of adults) phenotype. When accurately matched for age and obesity, only LADA patients with anti-GAD antibodies, but not GAD-negative/ CD38-positive patients, have reduced in vivo beta-cell function in comparison to antibody-negative patients. Transgenic mice overexpressing CD38 show enhanced glucose-induced insulin release, whereas, conversely, CD38 knockout mice display a severe impairment in beta-cell function. Few Japanese diabetic patients carry a missense mutation in the CD38 gene; in Caucasian patients mutations in the CD38 gene have not been found. Collectively, these findings suggest that activation of CD38 represents an alternative signaling pathway for glucose-induced insulin secretion in human beta-cells. More information, however, is necessary to gauge the role of CD38 autoimmunity in the context of the natural history of human Type 1 or Type 2 diabetes.
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PMID:CD38 autoimmunity: recent advances and relevance to human diabetes. 1550 98

Both protein kinase C (PKC) activation and increased oxidative stress have been paid attention to as important causative factors for diabetic vascular complications. In this article, we show a PKC-dependent increase in oxidative stress in vascular tissues of diabetes and insulin resistant state. High glucose level and free fatty acids stimulate de novo diacylglycerol (DAG)-PKC pathway and subsequently stimulate reactive oxygen species (ROS) production through a PKC-dependent activation of NAD(P)H oxidase. Increasing evidence has also shown that NAD(P)H oxidase components are upregulated in micro- and macro- vascular tissues of animal models and patients of diabetes and obesity. It is also noted that increased intrinsic angiotensin II production may amplify such a PKC-dependent activation of NAD(P)H oxidase in diabetic vascular tissues. These mechanisms may play an important role in the diabetic vascular complications and the accelerated atherosclerosis associated with diabetes and obesity. In addition, recent reports have shown that NAD(P)H oxidases exist in pancreatic beta-cells and adipocytes, and this oxidase-generated ROS production may play an important role in both the progressive beta-cell dysfunction and the dysregulated adipocytokine production and subsequent obesity-induced metabolic syndrome. These results suggest that an NAD(P)H oxidase activation may be a useful therapeutic target for preventing diabetic vascular complications, progressive beta-cell dysfunction and metabolic syndrome.
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PMID:NAD(P)H oxidase activation: a potential target mechanism for diabetic vascular complications, progressive beta-cell dysfunction and metabolic syndrome. 1602 68


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