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)

The response of rat gastrocnemius muscle fibers to chronic streptozotocindiabetes was studied. Transverse sections of this muscle from normal and diabetic rats were histochemically assayed for reduced diphosphopyridine nucleotide-diaphorase, myofibrillar adenosine triphosphatase, mitochondrial alpha-glycerophosphate dehydrogenase, beta-hydroxybutyrate dehydrogenase, and alkaline phosphatase activities. Cross-sectional areas of the fiber types were measured, and fiber capillarization and populations estimated. Chemically-induced diabetes appeared to have little effect on the metabolic or morphological properties of slow-twitch fibers. However, a general dedifferentiation occurred in the 2 fast-twitch fiber populations. There was a loss of oxidative potential in the fast-twitch-oxidative-glycolytic fibers, and a significant decrease in size in the fast-twitch-glycolytic fibers. No change in the proportions of slow- and fast-twitch fibers in the muscles of diabetic rats occurred. It is concluded that hypoinsulinism has differential effects on the 3 fiber types in heterogeneous rat skeletal muscle, and that slow-twitch fibers are least affected by the diabetic condition.
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PMID:Histochemical properties of skeletal muscle fibers in streptozotocin-diabetic rats. 12 6

Pyruvate dehydrogenase (PDH), alpha-keto glutarate dehydrogenase (alpha-KGDH) and lipoamide dehydrogenase (LAD) were measured in platelets of 11 patients with typical Friedreich's ataxia and 10 normal control subjects. Serum LAD was also evaluated in the same patients. No statistically significant changes were found in platelets for the group as a whole, although some patients had low values (more than one standard deviation below control mean). Serum LAD was significantly reduced in the patients with Friedreich's ataxia. This was not due to associated diabetes.
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PMID:Serum and platelet lipoamide dehydrogenase in Friedreich's ataxia. 64 85

A film test for the rapid detection of plasma/serum 3-hydroxybutyrate (3-OHB) has been developed. The film contains NAD, nitro blue tetrazolium, 3-OHB dehydrogenase, and diaphorase, and the surface is coated with modified biomembrane and can detect 50-1500 microM 3-OHB within 2-3 min. One drop or 50 microliters of plasma/serum or blood is applied to the film, and the violet color is read via reflectance meter after 2 min. Plasma/serum samples greater than 1500 microM 3-OHB can be measured by dilution with saline. In blood with 40% hematocrit, the color developed is 50% less than with plasma/serum, and this was adjusted in the reflectance meter. A good correlation (r = 0.99) was observed between results with automated and film methods and between visual methods and reflectance meter. In insulin-dependent diabetes mellitus, all 3 subjects with positive ketonuria (+ +), 8 of 12 subjects with mild ketonuria (+), and 7 of 25 subjects without ketonuria exhibited elevation of 3-OHB in blood greater than 200 microM. The results indicate that 3-OHB film is valuable not only in the emergency room for the differential diagnosis between ketoacidotic and nonketotic hypersomolar coma but also as a marker for insulin dependency, energy dependency on fatty acid compared with glucose, and metabolic control of diabetes.
Diabetes Care 1990 May
PMID:Development of stable film test for rapid estimation of blood or plasma 3-hydroxybutyrate. 235 Oct 30

Lipoic acid (alpha-lipoic acid, thioctic acid) is applied as a therapeutic agent in various diseases accompanied by polyneuropathia such as diabetes mellitus. The stereoselectivity and specificity of lipoic acid for the pyruvate dehydrogenase complex and its component enzymes from different sources has been studied. The dihydrolipoamide dehydrogenase component from pig heart has a clear preference for R-lipoic acid, a substrate which reacts 24 times faster than the S-enantiomer. Selectivity is more at the stage of the catalytic reaction than of binding. The Michaelis constants of both enantiomers are comparable (Km = 3.7 and 5.5 mM for R- and S-lipoic acid, respectively) and the S-enantiomer inhibits the R-lipoic acid dependent reaction with an inhibition constant similar to its Michaelis constant. When three lipoic acid homologues were tested, RS-1,2-dithiolane-3-caproic acid was one carbon atom longer than lipoic acid, while RS-bisnorlipoic acid and RS-tetranorlipoic acid were two and four carbon atoms shorter, respectively. All are poor substrates but bind to and inhibit the enzyme with an affinity similar to that of S-lipoic acid. No essential differences with respect to its reaction with lipoic acid enantiomers and homologues exist between free and complex-bound dihydrolipoamide dehydrogenase. Dihydrolipoamide dehydrogenase from human renal carcinoma has a higher Michaelis constant for R-lipoic acid (Km = 18 mM) and does not accept the S-enantiomer as a substrate. Both enantiomers of lipoic acid are inhibitors of the overall reaction of the bovine pyruvate dehydrogenase complex, but stimulate the respective enzyme complexes from rat as well as from Escherichia coli. The S-enantiomer is the stronger inhibitor, the R-enantiomer the better activator. The two enantiomers have no influence on the partial reaction of the bovine pyruvate dehydrogenase component, but do inhibit this enzyme component from rat kidney. The implications of these results are discussed.
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PMID:Interaction of alpha-lipoic acid enantiomers and homologues with the enzyme components of the mammalian pyruvate dehydrogenase complex. 766 66

The effect of R, S, and racemic forms of a-lipoic acid was tested on the formation of opacity in normal rat lenses incubated with 55.6 mM glucose, as a model for in vivo diabetic cataractogenesis. Control lenses, incubated 8 days with 5.56 mM glucose, did not develop opacities. Formation of lens opacities in vitro was correlated with lactate dehydrogenase (LDH) leakage into the incubation medium. Opacity formation and LDH leakage, resulting from incubation in medium containing 55.6 mM glucose to model diabetes, were both suppressed by the addition of 1 mM R-lipoic acid. Addition of 1 mM racemic lipoic acid reduces these damaging effects to the lens by one-half, while S-lipoic acid potentiated LDH leakage, consistent with the hypothesis that R-lipoic acid is the active form. Although HPLC analysis demonstrated that both stereoisomers of lipoic acid were reduced to dihydrolipoate at comparable rates by the intact lens, the mitochondrial lipoamide dehydrogenase system is highly specific for reduction of exogenous R-lipoic to dihydrolipoic acid. Therefore, stereospecific protection against this opacity is consistent with specific reduction of R-lipoic acid in mitochondria of the vulnerable cells at the lens equator where the first globular degeneration is seen in glucose cataract.
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PMID:Modelling cortical cataractogenesis 17: in vitro effect of a-lipoic acid on glucose-induced lens membrane damage, a model of diabetic cataractogenesis. 867 20

Diabetes mellitus leads to micro- and macroangiopathy with endothelial dysfunction. To investigate the direct influence of high glucose on endothelial cell structure and possible pharmacologic effects, seven different experimental protocols were carried out on endothelial cells in culture. There were four control groups with either 5 mM D-glucose alone, 5 mM D-glucose plus 15 mM L-glucose (for osmotic control), 5 mM D-glucose plus 500 nM celiprolol, or 5 mM D-glucose plus 57 nM nitrendipine. Three experimental groups had either 20 mM D-glucose alone, 20 mM D-glucose plus 500 nM celiprolol or 20 mM D-glucose plus 57 nM nitrendipine. Treatment of all groups started at the third passage of the cells and lasted until confluence was reached (5-8 days). The endothelial cells were fixed in paraformaldehyde and stained either with hematoxylin-eosin solution, with nitro blue tetrazolium for nicotinamide adenine dinucleotide phosphate (NADPH)- diaphorase staining, or actin staining with phalloidin was carried out. For quantitative analysis of the histologic specimens, the slides were viewed via a microscope and a videocamera. The pictures were converted digitally and could be analyzed with the videopicture-analyzing system, JAVA. In the four control groups, neither treatment with 15 mM L-glucose nor administration of celiprolol or nitrendipine had an effect on cell, cytoplasm, and nuclear area. The number of giant or polynuclear cells and the histochemical NADPH-diaphorase activity were not altered. Incubation of endothelial cells with 20 mM D-glucose for 5-8 days resulted in a significant increase in total and cytoplasmic area, as well as in the number of giant and polynuclear cells, whereas the nuclear area and the NADPH-diaphorase activity were significantly reduced. Concomitant treatment with celiprolol was able to reverse these alterations in endothelial structure significantly but had only a weak effect on the NADPH-diaphorase. Nitrendipine had no beneficial effect on the high D-glucose-induced cell alterations. The actin staining of the control cells showed the typical actin pattern with most of the actin filaments arranged at the periphery of the cells. Administration of 20 mM D-glucose resulted in a disturbance of the actin pattern, with most of the actin filaments now arranged in the middle of the cells. However, neither celiprolol nor nitrendipine exhibited a significant influence on this altered actin structure. High D-glucose treatment over several days thus leads to severe changes in endothelial cell structure, and celiprolol may have a beneficial effect on these hyperglycemia-induced cell alterations.
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PMID:High D-glucose induces alterations of endothelial cell structure in a cell-culture model. 926 45

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

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


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