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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previous studies have shown that nitric oxide synthase (NOS), the enzyme that catalyzes the formation of nitric oxide (NO), is expressed in skeletal muscle. The aim of the present study was to test the hypothesis that NO can modulate glucose metabolism in slow- and fast-twitch skeletal muscles. Calcium-dependent NOS was detected in skeletal muscle, and the enzyme activity was greater in fast-type extensor digitorum longus (EDL) muscles than in slow-type soleus muscles. Both the neuronal-type (nNOS) and endothelial-type (eNOS) enzymes are expressed in resting skeletal muscles. However, nNOS protein was only detected in EDL muscles, whereas eNOS protein contents were comparable in soleus and EDL muscles. NOS expression in muscle cryosections (diaphorase histochemistry) was located in vascular endothelium and in muscle fibers, and the staining was greater in type IIb than in type I and IIa fibers. The macrophage-type inducible NOS (iNOS) was not detected in resting muscle, but endotoxin treatment induced its expression, concomitant with elevated NO production. iNOS induction was associated with impaired insulin-stimulated glucose uptake in isolated rat muscles. In vitro, NOS blockade with specific inhibitors did not affect basal or insulin-stimulated glucose transport in EDL or soleus muscles. In contrast, the NO donors GEA 5024 and sodium nitroprusside induced dose-dependent inhibition (up to 50%) of maximal insulin-stimulated glucose transport in both muscles with minor effects on basal uptake values. GEA 5024 also blunted insulin-stimulated glucose transport and amino acid uptake in cultured L6 muscle cells without affecting insulin binding to its receptor. On the other hand, the permeable cGMP analogue dibutyryl cGMP did not affect muscle glucose transport. These results strongly suggest that NO modulates insulin action in both slow- and fast-type skeletal muscles. This novel autocrine action of NO in muscle appears to be mediated by cGMP-independent pathways.
Diabetes 1997 Nov
PMID:Expression of nitric oxide synthase in skeletal muscle: a novel role for nitric oxide as a modulator of insulin action. 935 14

The purpose of this work was to study the neurons of the myenteric plexus of the cecum of rats with chronic streptozotocin-induced diabetes. We used four experimental groups of animals. In groups D2 and D8 animals were killed two and eight months, respectively, after diabetes induction and groups C2 and C8 were used as controls. We carried out whole-mount preparations stained with Giemsa and NADH-diaphorase. We verified that the diabetes did not alter the shape and disposition of the myenteric ganglia; it provoked decrease on the neuronal density and increase on the incidence of weakly basophilic neurons. The effects of streptozotocin caused dilatation of the cecum still evidenced two months after induction, but no more observed on the eight months after induction. The smaller incidence of neurons in group D8 relative to group C8 was due to the early loss related to the drug toxicity and later to the aging in diabetic condition.
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PMID:Morphological and quantitative analysis of the neurons of the myenteric plexus of the cecum of streptozotocin-induced diabetic rats. 962 27

To investigate the prevalence of mitochondrial DNA mutations among Japanese children with IDDM as well as in those with NIDDM, a total of 155 patients with IDDM and 30 patients with NIDDM who were younger than 15 years of age at onset were studied for the following mtDNA mutations: 1) the A-->G mutation at position 3243 of mitochondrial leucine transfer RNA (3243 mutation); 2) the G-->A mutation at position 3316 of mitochondrial leucine transfer RNA (3316 mutation), and 3) The T-->C mutation at position 3394 of the mitochondrial NADH dehydrogenase subunit (3394 mutation). None of the 155 IDDM patients had the 3243 mutation. Although two of the 155 IDDM patients had homoplasmy of 3316 and five had 3394 mutations, these frequencies were not significant compared with healthy controls. None of the 30 NIDDM patients had the 3243, 3316 or 3394 mutation. The presence of these mutations even in control subjects suggests that the effect of the 3316 or 3394 mutation on mitochondrial function is relatively mild. It seems that 3316 and 3394 mutations contribute to the manifestation of diabetes together with other genetic and/or environmental factors.
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PMID:The prevalence of mitochondrial gene mutations in childhood diabetes in Japan. 1039 45

This study had as its purpose to assess the effects of acute diabetes induced by streptozotocin (35 mg/kg body weight) on the number and size of the myenteric neurons of the duodenum of adult rats considering equally the antimesenteric and intermediate regions of the intestinal circumference. Experimental period extended for a week. Neuronal counts were carried out on the same number of fields of both regions of the duodenal circumference and measurements of neuronal and nuclear areas on equal numbers of cells. Number and size of the myenteric neurons stained with Giemsa were not significantly different between groups. On the other hand, the proportion of NADH-positive neurons increased from 18.54% on the controls to 39.33% on the diabetics. The authors discuss that this increased reactivity probably results from a greater NADH/NAD+ ratio, described in many tissues of diabetic animals, which has consequences on the modulation of the enzymes that use these cofactors and whose activity is detected by the NADH-diaphorase technique.
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PMID:Number and size of myenteric neurons of the duodenum of adult rats with acute diabetes. 1075 7

The purpose of the present study was to investigate the morphological and quantitative alterations of the myenteric plexus neurons of the stomach of rats with streptozotocin-induced chronic diabetes and compare them to those of non-diabetic animals. Samples from the body of the stomach were used for whole-mount preparations stained with NADH-diaphorase and for histological sections stained with hematoxylin-eosin. It was observed that diabetes cause a significant decrease on the number of neurons.
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PMID:Quantitative study of the myenteric plexus of the stomach of rats with streptozotocin-induced diabetes. 1129 31

Evidence is presented showing that a neuronal isoform of nitric oxide synthase (NOS) is expressed in rat pancreatic islets and INS-1 cells. Sequencing of the coding region indicated a 99.8% homology with rat neuronal NOS (nNOS) with four mutations, three of them resulting in modifications of the amino acid sequence. Double-immunofluorescence studies demonstrated the presence of nNOS in insulin-secreting beta-cells. Electron microscopy studies showed that nNOS was mainly localized in insulin secretory granules and to a lesser extent in the mitochondria and the nucleus. We also studied the mechanism involved in the dysfunction of the beta-cell response to arginine and glucose after nNOS blockade with N(G)-nitro-L-arginine methyl ester. Our data show that miconazole, an inhibitor of nNOS cytochrome c reductase activity, either alone for the experiments with arginine or combined with sodium nitroprusside for glucose, is able to restore normal secretory patterns in response to the two secretagogues. Furthermore, these results were corroborated by the demonstration of a direct enzyme-substrate interaction between nNOS and cytochrome c, which is strongly reinforced in the presence of the NOS inhibitor. Thus, we provide immunochemical and pharmacological evidence that beta-cell nNOS exerts, like brain nNOS, two catalytic activities: a nitric oxide production and an NOS nonoxidating reductase activity, both of which are essential for normal beta-cell function. In conclusion, we suggest that an imbalance between these activities might be implicated in beta-cell dysregulation involved in certain pathological hyperinsulinic states.
Diabetes 2001 Jun
PMID:A neuronal isoform of nitric oxide synthase expressed in pancreatic beta-cells controls insulin secretion. 1137 31

We have investigated by immuno-electron microscopy the presence of phosphotyrosine in cells as a whole and in different cell districts (nucleus, cytoplasm, plasma membrane, and mitochondria) in peripheral blood lymphocytes of IDDM (insulin-dependent diabetes mellitus) patients and age-matched controls. Immuno-gold particle density was highest in mitochondria and decreased in cytoplasm, nucleus and plasma membrane. The time dependence of phosphotyrosine labelling after cell isolation was very strong in all subcellular populations, with a fall in immunogold staining after 30 min. Staining levels at zero time were similar in controls and IDDM patients; the loss of phosphotyrosine labelling was much stronger in controls, except in the plasma membrane. Plasma membrane NADH oxidoreductase activity, studied using cytosolic NADH as substrate and assayed with DCIP as acceptor, was significantly increased in IDDM patients, suggesting a response to a deficient mitochondrial energetic activity. The fact that NADH oxidoreductase is a growth factor related to tyrosine phosphorylation pathways raises intriguing questions on the cellular derangement occurring in peripheral lymphocytes in IDDM, although the relationships among the immunocytochemical and biochemical changes is still obscure.
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PMID:Lymphocyte dysmetabolism: an immunocytochemical comparative approach in IDDM and control subjects. 1141 69

Experiments were performed to test the hypothesis that diabetes mellitus disrupts the balance between synthesis and degradation of nitric oxide (NO) in the renal cortex. Diabetes was induced by injection of streptozotocin, and sufficient insulin was provided to maintain moderate hyperglycemia for the ensuing 2 wk. Despite an 80% increase in total NO synthase activity measured by L-citrulline assay, nicotinamide adenine dinucleotide phosphate-diaphorase staining was unaltered, and no changes in NO synthase isoform protein levels or their distribution were evident in renal cortex from diabetic rats. Superoxide anion production was accelerated twofold in renal cortical slices from diabetic rats, with an associated 50% increase in superoxide dismutase activity. Western blots prepared by use of a monoclonal antinitrotyrosine antibody revealed an approximately 70-kD protein in renal cortex from sham rats, the nitrotyrosine content of which was threefold greater in cortical samples from diabetic rats. These observations indicate that the early stage of diabetes mellitus provokes accelerated renal cortical superoxide anion production in a setting of normal or increased NO production. This situation can be expected to promote peroxynitrite formation, resulting in the tyrosine nitration of a single protein of unknown identity, as well as a decline in the bioavailability of NO. These events are consistent with the postulate that oxidative stress promotes NO degradation in the renal cortex during the early stage of diabetes mellitus.
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PMID:Nitric oxide synthesis and oxidative stress in the renal cortex of rats with diabetes mellitus. 1146 35

A number of novel genes that are up-regulated in diabetic kidneys have been identified. Recently, transforming growth factor-beta (TGF-beta)--driven secreted proteins, i.e., connective tissue growth factor (CTGF) and gremlin, were identified. They are up-regulated in kidneys of diabetic animals and modulate the biology of mesangial cells. CTGF mediates TGF-beta--induced matrix overproduction by the mesangial cells. Gremlin is a putative antagonist of bone morphogenetic protein-2 that blocks mesangial cell proliferation. Thus, gremlin may modulate the biology of mesangium by stimulating mesangial cell proliferation and in turn production of matrix. In addition, transcriptionally regulated kinases, serum glucocorticoid-regulated kinase and munc-13 have been identified. The former stimulates renal tubular Na+ transport and is involved in hyperfiltraion of diabetic kidneys by a Na+ transport feedback mechanism. Munc-13 has been shown to induce apoptosis in hyperglycemic state via diacylglycerol-activated, PKC-independent signaling pathway. Another pathway relevant to diabetic nephropathy is polyol pathway, where glucose is reduced to sorbitol by aldose reductase. Recently, a renal-specific reductase of the aldo-keto reductase family was isolated. It is up-regulated in diabetic mice, and this could serve as a suitable target for gene therapy in renal complications of diabetes. Several mitochondrial genome-encoded genes, such as, cytochrome oxidase and NADH dehydrogenase, are up-regulated in diabetic kidneys. A novel nuclear-encoded mitochondrial gene, i.e., translocase inner mitochondrial membrane 44 (Tim44), is up-regulated in diabetic kidneys, and it may also serve as another target for molecular therapeutic intervention at the core storage energy sites, i.e., mitochondria. In this review, these novel differentially regulated genes that respond to hyperglycemic stress are described, and they may serve as possible targets for gene therapy in the treatment of diabetic nephropathy.
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PMID:Gene expression and identification of gene therapy targets in diabetic nephropathy. 1184 17

Neuronal nitric oxide is a non-adrenergic non-cholinergic neurotransmitter in the enteric nervous system and plays a role in a variety of enteropathies including Crohn's and Chagas' diseases, ulcerative colitis, diabetes, atrophy and hypertrophy. The content of neuronal nitric oxide synthase (nNOS) in the colon and the caecum from pigs infected with Schistosoma japonicum was studied using immunohistochemical and histochemical staining for nNOS and nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-diaphorase), respectively. In the infected pigs, lightly, moderately and less severely inflamed tissues showed increased nNOS and NADPH-diaphorase activities in nerve cell bodies and nerve fibres in the enteric plexuses compared to control pigs. There was a significant increase in the nerve cell body density of nNOS immunoreactive nerve cell bodies in the inner submucous plexus, outer submucous plexus and in the myenteric plexus. More intensely stained nerve cell bodies and varicosities were observed in tissue from prenatally infected and prenatally infected, postnatally re-infected pigs compared to postnatally infected pigs. However, the latter showed the highest numerical density of nNOS immunoreactive nerve cell bodies. Marked increases were seen in the inner submucous plexus followed by myenteric plexus, inner circular muscle, outer submucous plexus and mucous plexus. However, in very severe inflamed tissues, the number and staining intensity of nerve cell bodies and nerve fibre varicosities were reduced in plexuses located in the lesions with the inner submucous and mucous plexuses being the most affected. There was no staining in the nervous tissue within the eosinophilic cell abscesses and productive granulomas. The apparent alterations in the activities of enzymes responsible for the generation of nitric oxide (NO) show possible alterations in the NO mediated non-adrenergic non-cholinergic reflexes in the enteric nervous tissue. These alterations might contribute to impaired intestinal motility and absorption, and other pathophysiological conditions seen during S. japonicum infections.
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PMID:Neuronal nitric oxide synthase activity is increased during granulomatous inflammation in the colon and caecum of pigs infected with Schistosoma japonicum. 1217 Dec 50


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