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)

Semicarbazide-sensitive amine oxidase (SSAO) is located in the vascular smooth muscles, retina, kidney and the cartilage tissues, and it circulates in the blood. The enzyme activity has been found to be significantly increased in blood and tissues in diabetic patients and animals. Methylamine and aminoacetone are endogenous substrates for SSAO. The deaminated products are formaldehyde and methylglyoxal respectively, as well as H2O2 and ammonia, which are all potentially cytotoxic. Formaldehyde and methylglyoxal are cytotoxic towards endothelial cells. Excessive SSAO-mediated deamination may directly initiate endothelial injury and plaque formation, increase oxidative stress, which can potentiate oxidative glycation, and/or LDL oxidation and damage vascular systems. Formaldehyde is also capable of exacerbating advanced glycation, and thus increase the complexity of protein cross-linking. Uncontrolled SSAO-mediated deamination may be involved in the acceleration of the clinical complications in diabetes.
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PMID:Deamination of methylamine and angiopathy; toxicity of formaldehyde, oxidative stress and relevance to protein glycoxidation in diabetes. 956 20

To measure myocardial blood flow, Nitrogen-13 ammonia. Oxygen-15 water, Rubidium-82 and et al. are used. Each has merit and demerit. By measuring myocardial coronary flow reserve, the decrease of flow reserve during dipyridamole in patients with hypercholesterolemia or diabetes mellitus without significant coronary stenosis was observed. The possibility of early detection of atherosclerosis was showed. As to myocardial metabolism, glucose metabolism is measured by Fluorine-18 fluorodexyglucose (FDG), and it is considered as useful for the evaluation of myocardial viability. We are using FDG to evaluate insulin resistance during insulin clamp in patients with diabetes mellitus by measuring glucose utilization rate of myocardium and skeletal muscle. FFA metabolism has been measured by 11C-palmitate, but absolute quantification has not been performed. Recently the method for absolute quantification was reported, and new radiopharmaceutical 18F-FTHA was reported. Oxygen metabolism has been estimated by 11C-acetate. Myocardial viability, cardiac efficiency was evaluated by oxygen metabolism. As to receptor or sympathetic nerve end, cardiac insufficiency or cardiac transplantation was evaluated. Imaging of positron emitting radiopharmaceutical by gamma camera has been performed. Collimator method is clinically useful for cardiac imaging of viability study.
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PMID:[The review of myocardial positron emission computed tomography and positron imaging by gamma camera]. 964 28

The most common use of artificial cells is for bioencapsulation of biologically active materials. Each artificial cell can contain combinations of materials. The permeability, composition and shape of an artificial cell membrane can be varied using different types of synthetic or biological materials. These possible variations in contents and membranes allow for large variations in the properties and functions of artificial cells. Artificial cells containing adsorbents have been a routine form of treatment in hemoperfusion for patients. This includes acute poisoning, high blood aluminum and iron, and supplement to dialysis in kidney failure. Artificial red blood cell substitutes based on modified hemoglobin are already in Phase I and Phase II clinical trials in patients. Artificial cell encapsulated cell cultures are being studied for the treatment of diabetes, liver failure, gene therapy and other conditions. Research on artificial cells containing enzymes includes their use for treatment in hereditary enzyme deficiency diseases and other diseases. Recent demonstration of extensive enterorecirculation of amino acids in the intestine has allowed oral administration to deplete specific amino acids. One example is phenylketonuria, an inborn error or metabolism resulting in high systemic phenylalanine levels. Preliminary clinical studies in patients using bioencapsulation of cells or enzymes have started. Artificial cells containing complex enzyme systems convert wastes like urea and ammonia into essential amino acids. Artificial cells are being used for the production of monoclonal antibodies, interferon and other biotechnological products. Other areas of biotechnological uses include drug delivery, and other areas of biotechnology, chemical engineering and medicine.
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PMID:Artificial cells with emphasis on bioencapsulation in biotechnology. 970 91

Ischemic myocardium avidly incorporates fluorine-18 fluorodeoxyglucose (F-18 FDG) in the fasting state, in contrast to the relative absence of F-18 FDG uptake in normal myocardium with sufficient blood flow in the fasting state. Although many studies have attempted to use F-18 FDG uptake to discriminate ischemic but viable myocardium from scarred myocardium, little is known clinically about the correlation between blood flow and F-18 FDG uptake in ischemic myocardium. We studied the critical level of blood flow that causes avid F-18 FDG uptake in myocardium in 9 patients. All patients had angiographically proven ischemic heart disease but no diabetes. Regional myocardial blood flow (RMBF) was measured quantitatively by positron emission tomography (PET) using nitrogen-13 ammonia in the resting state, in which the normal value was 80.2 +/- 13.0 ml/min/100 cm3. The F-18 FDG uptake in myocardium was assessed with the differential uptake ratio (DUR) scale. We constructed circumferential profiles of radioactivity uptake in myocardium for each study, and chose 780 sections of myocardium in which the relation between the two factors could be analyzed. In moderately ischemic to normal myocardium with RMBF of 50 to 90 ml/min/100 cm3, RMBF and F-18 FDG uptake were negatively correlated (r = -0.44, p < 0.01). When RMBF was 50 to 60 ml/min/100 cm3 (n = 121), the peak DUR value of F-18 FDG uptake was 4.0 +/- 2.0. The two factors were not correlated when RMBF was less than 50 ml/min/100 cm3 or 90 ml/min/100 cm3 or higher. Our results suggest that RMBF and F-18 FDG uptake values as measured with PET may provide valuable information on the possible benefit of intervention in ischemic heart disease.
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PMID:Correlation between myocardial blood flow and fasting glucose metabolism in ischemic heart disease. Quantitative assessment by nitrogen-13 ammonia and fluorine-18 fluorodeoxyglucose positron emission tomography. 971 Nov 79

We report herein the case of a 39-year-old man with cirrhosis of the liver who developed hepatic encephalopathy and progressive diabetes caused by a pancreatic siphon after undergoing a distal splenorenal shunt (DSRS) for a variceal hemorrhage. Radiologic occlusion was judged to be inappropriate because of the extensive DSRS. The DSRS was surgically closed 6 years after the operation to restore portal perfusion. To alleviate the portal hypertension, splenectomy and gastric devascularization were performed, which proved successful, as the encephalopathy disappeared completely, the ammonia levels decreased, liver function improved, and the diabetes subsided. Our experience indicates that a small percentage of cirrhotic patients who undergo DSRS with longterm followup may develop various undesirable complications, although some of these patients benefit from a combination of surgical shunt occlusion, splenectomy, and gastric devascularization.
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PMID:Successful surgical treatment for hepatic encephalopathy caused by a pancreatic siphon: report of a case. 978 82

Plasma semicarbazide-sensitive amine oxidase is raised in patients with Type I (insulin-dependent) diabetes mellitus. It has been suggested that this enzyme is involved in the development of microvascular damage through its ability to convert amines (e.g. methylamine and aminoacetone) into aldehydes, hydrogen peroxide and ammonia. Plasma semicarbazide-sensitive amine oxidase was found to be equally raised both in patients with Type I diabetes (n = 73) and Type II (non-insulin-dependent) diabetes mellitus (n = 88) compared with control subjects (621 +/- 209 and 619 +/- 202 vs 352 +/- 102 mU/l, p < 0.0001) and to correlate in multiple regression analysis with HbA1c. Since the enzyme could protect the islets from the inhibitory effects of methylamine on insulin secretion, we also tested sera of 100 children, collected consecutively at first diagnosis of Type I diabetes, for semicarbazide-sensitive amine oxidase. The activity was greatly increased compared with serum values of 76 control (siblings) children (757 +/- 300 vs 455 +/- 138 mU/l, p < 0.0001), but not associated with HbA1c. Our study confirms the increase of plasma semicarbazide-sensitive amine oxidase in Type I diabetes and extends this finding to Type II diabetes as well as to childhood Type I at first clinical diagnosis. In the last case increased enzyme activities could serve to protect the islets from inhibitory effects of methylamine but cause damage by generation of hydrogen peroxide, aldehydes and ammonia. In the long run the increased enzyme activities could also contribute to vascular damage by direct cytotoxic action on endothelial cells, including increased oxidative stress and glycosylation of proteins.
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PMID:Circulating semicarbazide-sensitive amine oxidase is raised both in type I (insulin-dependent), in type II (non-insulin-dependent) diabetes mellitus and even in childhood type I diabetes at first clinical diagnosis. 1006 4

Leucine or the nonmetabolized leucine analog +/- 2-amino-2-norbornane-carboxylic acid (BCH) (both at 10 mmol/l) induced biphasic insulin secretion in the presence of 2 mmol/l glutamine (Q2) in cultured mouse islets pretreated for 40 min without glucose but with Q2 present. The beta-cell response consisted of an initial peak of 20- to 25-fold above basal and a less marked secondary phase. However, BCH produced only a delayed response, while leucine was totally ineffective when islets were pretreated with 25 mmol/l glucose plus Q2. With Q2, 10 mmol/l BCH or leucine caused a nearly threefold increase, a twofold increase, or had no effect on cytosolic Ca2+ levels in islets pretreated for 40 min with 0, 5, or 15 mmol/l glucose, respectively. Thus, pretreatment of islets with high glucose inhibited BCH- and leucine-induced cytosolic Ca2+ changes and insulin release. Glucose decreased glutamine oxidation in cultured rat islets when BCH was present at 10 mmol/l, but not in its absence, with a lowest effective level of approximately 0.1 mmol/l, a maximum of 18-30 mmol/l, and an inhibitory concentration, 50%, of approximately 3 mmol/l. The data are consistent with the hypothesis that glucose inhibits glutaminolysis in pancreatic beta-cells in a concentration-dependent manner and hence blocks leucine-stimulated insulin secretion. We postulate that in the basal interprandial state, glutaminolysis of beta-cells is partly turned on because glutamate dehydrogenase (GDH) is activated by a decreased P-potential due to partial fuel depletion and sensitization to endogenous activators such as leucine. Additionally, it may contribute significantly to basal insulin release, which is known to be responsible for about half of the insulin released daily. The data explain "leucine-hypersensitivity" of beta-cells during hypoglycemia and contribute to the elucidation of the GDH-linked syndrome of hyperinsulinism associated with elevated serum ammonia levels. Thus, understanding the precise regulation and role of beta-cell glutaminolysis is probably central to our concept of normal blood glucose control.
Diabetes 1999 Aug
PMID:Glucose regulation of glutaminolysis and its role in insulin secretion. 1042 70

We reported a case of adult-onset citrullinemia associated with hypertrigliceridemia and diabetes mellitus. A 24-year-old female was healthy until recently. She first felt intermittent headaches and nausea. Then she noticed memory loss and tiredness. Abnormal behavior such as getting lost on the way from her company sometimes occurred. She came to our hospital because these symptoms had been getting worse. Neurologically she had a very mild disturbed consciousness. An EEG recording showed diffuse slow wave with high amplitude. MR image of the brain showed hyper-intensity in globus pallidus with T1-weighted image. Plasma citrullin level was very high. Plasma ammonia and triglyceride showed a moderately high level. Using biopsied liver tissues, the enzymes of the urea cycle were analyzed. Argininosuccinate synthetase activity was extremely low. Because of clinical course and the result of liver biopsy, the patient was diagnosed as type 2 citrullinemia. A low protein diet was started, but intermittent nausea and consciousness disturbance did not improve. A partial liver transplantation was performed. The living donor was her father, a 50-year-old male, who had normal liver function. After the liver transplantation, all neurological signs soon disappeared. Plasma citrulline, ammonia and triglyceride normalized rapidly. An EEG recording became normal, and the hyper-intensity in globus pallidus with T1-weighted MR image disappeared two months after surgery. Liver transplantation should be planned as soon as possible in a type 2 citrullinemia patient.
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PMID:[Liver transplantation in type II citrullinemia]. 1065 68

The liver shows net glutamine uptake after a protein-containing meal, during uncontrolled diabetes, sepsis and short-term starvation, but changes to net release during long-term starvation and metabolic acidosis. Some studies report a small net release of glutamate by the liver. The differential expression of glutamine synthetase (perivenous) and glutaminase (periportal) within the liver indicates that glutamine is used for urea synthesis in periportal cells, whereas glutamine synthesis serves to detoxify any residual ammonia in perivenous cells. Experiments in vivo suggest that changes in net hepatic glutamine balance are due predominantly to regulation of glutaminase activity, with the flux through glutamine synthetase being relatively constant.
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PMID:Glutamine and glutamate metabolism across the liver sinusoid. 1073 66

Positron emission tomography (PET) is the most advanced scintigraphic imaging technique developed for in-vivo assessment of cardiac physiology and biochemistry. The currently available PET technology allows the measurement of regional tracer activity with high spatial and temporal resolution. Several radiopharmaceuticals have been introduced to study myocardial perfusion enabling accurate diagnosis and localization of coronary artery disease (CAD). Assessing myocardial blood flow at rest and under stress conditions and calculating (regional) coronary flow reserve by N-13 ammonia, Rb-82 or 0-15 water PET is the most sensitive means to detect any abnormal vasoreactivity which is already found at very early stages of the atherosclerotic process before any angiographic or clinical evidence of CAD. Flow tracers provide also quantitative information on the hemodynamic effects of any local, invasive (angioplasty) or systemic (risk factor modification) intervention. Metabolic imaging with F-18 deoxyglucose (FDG) PET represents currently the gold-standard for tissue viability assessment with well-validated information about the presence and extent of viable myocardium. The prognostic information of metabolic imaging extends to (preoperative) risk stratification in patients with congestive heart failure and facilitates the decision making between revascularization or conservative management. FDG has been also used in combination with SPECT providing comparable physiologic and pathophysiologic information but without need for the expensive and rarely available imaging technology of PET. More recently, newer tracers such as radiolabeled catecholamine analogs allowed the evaluation of cardiac autonomic innervation in a variety of cardiac diseases with involvement of neuronal innervation. C-11 hydroxyephedrine (HED) enabled imaging of alterations in neuronal innervation in diabetes, congestive heart failure and after heart transplantation. The unique functional and prognostic potential provided by PET imaging together with an expected easier access to this technology with better availability of lower cost instrumentation should raise its clinical acceptance in the near future.
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PMID:The clinical role of positron emission tomography in management of the cardiac patient. 1075 Apr 44


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