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  • 1
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: Diabetic neuropathy is a degenerative complication of diabetes accompanied by an alteration of nerve conduction velocity (NCV) and Na,K-ATPase activity. The present study in rats was designed first to measure diabetes-induced abnormalities in Na,K-ATPase activity, isoenzyme expression, fatty acid content in sciatic nerve membranes, and NCV and second to assess the preventive ability of a fish oil-rich diet (rich in n-3 fatty acids) on these abnormalities. Diabetes was induced by intravenous streptozotocin injection. Diabetic animals (D) and nondiabetic control animals (C) were fed the standard rat chow either without supplementation or supplemented with either fish oil (DM, CM) or olive oil (DO, CO) at a daily dose of 0.5 g/kg by gavage during 8 weeks. Analysis of the fatty acid composition of purified sciatic nerve membranes from diabetic animals showed a decreased incorporation of C16:1(n-7) fatty acids and arachidonic acids. Fish oil supplementation changed the fatty acid content of sciatic nerve membranes, decreasing C18:2(n-6) fatty acids and preventing the decreases of arachidonic acids and C18:1(n-9) fatty acids. Protein expression of Na,K-ATPase α subunits, Na,K-ATPase activity, and ouabain affinity were assayed in purified sciatic nerve membranes from CO, DO, and DM. Na,K-ATPase activity was significantly lower in sciatic nerve membranes of diabetic rats and significantly restored in diabetic animals that received fish oil supplementation. Diabetes induced a specific decrease of α1- and α3-isoform activity and protein expression in sciatic nerve membranes. Fish oil supplementation restored partial activity and expression to varying degrees depending on the isoenzyme. These effects were associated with a significant beneficial effect on NCV. This study indicates that fish oil has beneficial effects on diabetes-induced alterations in sciatic nerve Na,K-ATPase activity and function.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Clinica Chimica Acta 228 (1994), S. 161-170 
    ISSN: 0009-8981
    Keywords: Diabetes mellitus ; Microcalorimetry ; Na^+-K^+pump
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    General and Comparative Endocrinology 25 (1975), S. 313-322 
    ISSN: 0016-6480
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Medicine
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 0167-0115
    Keywords: alcohol ; pancreatic inhibition ; pancreatic polypeptide
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-0428
    Keywords: Type 1 diabetes ; tubulin ; microtubules ; anti-tubulin antibodies
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Antibodies to tubulin, the fundamental protein of microtubules, were studied by radioimmunoassay in patients with Type 1 (insulin-dependent) diabetes of varying duration and in healthy control subjects. Elevated levels of anti-tubulin antibodies were found in 46% of 28 patients with Type 1 diabetes of recent onset (⩽ 6 months) and in only 6.2% of 64 patients with long-standing Type 1 diabetes (duration 6–43 years). None of 34 DR3-positive normal subjects and none of 20 Type 2 (non-insulin-dependent) diabetic patients were positive for anti-tubulin antibodies. Anti-tubulin antibody levels were elevated in two out of 26 first-degree relatives of Type 1 diabetic patients. The specificity of the detection of anti-tubulin antibodies was demonstrated by (1) dilution of the sera, (2) competitive binding experiments between labelled and unlabelled tubulin, (3) immunoblotting. Antibodies to tubulin were elevated in 60% of patients with islet cell surface antibodies and there was a significant association between anti-tubulin antibodies and islet-cell surface antibodies. These antibodies, however, recognize different specificities, since adsorption of islet cell surface antibody by rat islets did riot alter the anti-tubulin antibody activity. Elevated anti-actin antibody responses were found in two out of 17 and one out of 26 patients with recent onset and long-standing Type 1 diabetes, respectively. In conclusion, anti-tubulin antibodies are detected in a high proportion of patients with diabetes of recent onset, are associated with islet cell surface antibodies and like islet cell surface antibodies decrease or disappear during the course of the disease. Therefore, elevation of antitubulin antibodies could represent another ‘marker’ of the immunological features of Type 1 diabetes. However, these findings, together with our previous observation of an elevation of anti-tubulin antibodies in autoimmune thyroid disorders, indicate a wider involvement of autoimmunity with tubulin and suggest that similar autoimmune phenomena could develop in Type 1 diabetes and some other diseases.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-0428
    Keywords: Nicotinamide ; Type 1 (Insulin-dependent) diabetes ; C-peptide ; residual insulin secretion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In vivo and in vitro experiments have shown that nicotinamide enhances the regeneration of rat B cells. Nicotinamide has been administered to human subjects at a dose of 3 g/day for more than one year without any serious side effects. A trial was conducted to study if nicotinamide could protect B cells in Type I (insulin-dependent) diabetic patients with established diabetes, but still with residual insulin secretion, the latter being evaluated throughout the study period. A randomized double-blind study was carried out on 26 Type I diabetic patients aged 15 to 40 years who had been treated with insulin for 1 to 5 years but who had a residual insulin secretion characterized by a glucagon stimulated C-peptide level higher than 0.1 nmol/l. They were given either 3 g/day of nicotinamide or a placebo for nine months. At baseline the treated and control groups did not differ according to age, diabetes duration, insulin dose, HbA1c or C-peptide levels. Three patients dropped out of the study. At 9 months there were no significant changes in the insulin doses required. However, HbA1c rose in the control group (8.1±0.4 vs 9.8±0.5%, p〈0.05) but not in the nicotinamide treated group (7.5±0.5 vs 6.9±0.4%). Insulin secretion deteriorated in the control patients (fasting C-peptide: 0.28±0.05 vs 0.12±0.03 nmol/l, p〈0.05; post glucagon C-peptide: 0.34±0.07vs 0.14±0.02, p〈0.05) but not in the treated patients (fasting C-peptide: 0.22±0.04 vs 0.24±0.05 nmol/l; post glucagon C-peptide: 0.30±0.04 vs 0.33±0.07). At six and nine months, fasting and stimulated C-peptide were higher in the treated than in the non-treated group. The C-peptide response to a meal test gradually declined in the placebo group, whereas it was stable in the nicotinamide treated group. No serious side effects were noted; in particular, hepatic function and plasma lipid content remained unchanged. These results suggest that nicotinamide treatment may protect residual B-cell function in Type 1 diabetes; but further studies are needed to assess the clinical implications of such treatment.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-0428
    Keywords: Plasminogen activator inhibitor 1 ; fibrinolysis ; atherosclerosis ; arterial thrombosis ; insulin ; insulin resistance ; low density lipoprotein ; hepatocytes ; endothelial cells
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary According to recent prospective studies, hypofibrinolysis due to elevated plasma plasminogen activator inhibitor 1 levels appears to be an independent risk factor for myocardial reinfarction in men, and hyperinsulinaemia, a major indicator of insulin resistance is considered as a risk factor for coronary disease. It has recently been shown that insulin resistance is accompanied by an increased plasma plasminogen activator inhibitor 1 concentration: A significant correlation coefficient was demonstrated between plasminogen activator inhibitor 1 and fasting plasma insulin in the normal population, in obese subjects, in Type 2 (non-insulin-dependent) diabetic patients and in angina pectoris. Attempts to decrease insulin resistance such as fasting, diet, or administration of an oral anti-diabetic drug such as Metformin induced a parallel decrease in plasma insulin and plasminogen activator inhibitor 1 levels. This inhibitor is produced by endothelial cells and by hepatocytes in culture. Plasminogen activator inhibitor 1 synthesis by hepatocytes in culture was stimulated by an increasing insulin concentration, or low density lipoproteins, whereas the endothelial cell synthesis was stimulated by very low density lipoproteins especially when they were obtained from hypertriglyceridaemic patients. Therefore, a direct effect of insulin or lipoprotein changes on the cells which synthesize plasminogen activator inhibitor 1 could be responsible for its increased plasma concentration in insulin resistance states. The increase in plasma plasminogen activator inhibitor 1 levels linked to hyperinsulinaemia is a tempting partial explanation for the association between insulin resistance and coronary disease.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1432-0428
    Keywords: Keywords Diabetes mellitus ; fish oil ; Na ; K-ATPase ; isoform ; mRNA ; fatty acid.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Diabetic cardiomyopathy has been associated with a decrease in Na,K-ATPase activity and expression, as well as alterations in membrane lipid composition. The aim of this study was twofold; 1) to document in rats the effect of streptozotocin-induced diabetes on myocardial Na,K-ATPase and fatty acids, and 2) to evaluate the potential effect of a dietary supplementation with fish oil (n-3 fatty acids) on the streptozotocin-induced changes. Assays were performed in purified cardiac plasma membranes to determine Na,K-ATPase activity, expression of the different α- and β-subunits of Na,K-ATPase, and the fatty acid content of total phospholipids. Relative abundance of the mRNAs encoding the α1, α2 and β1 isoforms was studied by Northern blot analysis. Results demonstrated that diabetes significantly decreased activities of α1 and α2 isoforms and mRNA levels of α2 and β1 isoforms, and, at the protein level, increased α1-isoforms and decreased both α2- and β1-isoforms. Changes in fatty acid content of the membrane were consistent with inhibition of desaturase. Fish-oil supplementation produced an increase in membrane incorporation of eicosapentaenoic acid. It also increased the level of β1-isoforms and restored the activity of the α2-isoenzyme without significant changes in the level of α1- and α2-isoforms. Northern blot analysis showed no effect of fish oil supplementation. Experimental diabetes and prevention by the fish oil rich (n-3 fatty acids) diet induced specific effects on the activity and expression of α and β Na,K-ATPase subunit isoforms. These studies suggest that fish oil therapy may be effective in preventing some of the adverse consequences of diabetes. [Diabetologia (1997) 40: 496–505]
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1432-0428
    Keywords: Keywords Na/K ATPase activity ; C-peptide ; Human erythrocyte ; Type I diabetes mellitus ; Type II diabetes mellitus.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Erythrocyte Na/K ATPase activity is decreased in Type I diabetic patients; for Type II diabetic patients, literature data are controversial. Therefore, we have compared this enzymatic activity in 81 patients with Type I diabetes mellitus, 87 with Type II diabetes mellitus and 75 control subjects. Mean erythrocyte Na/K ATPase activity was lower in the Type I diabetic patients (285 ± 8 nmol Pi · mg protein–1· h–1) than in the control subjects (395 ± 9 nmol Pi · mg protein–1· h–1) whereas that of the Type II diabetic patients did not differ from that of control subjects. Sex, age, body mass index, and HbA1 c levels did not influence erythrocyte Na/K ATPase activity. The 25 Type II diabetic patients treated with insulin, however, had lower Na/K ATPase activity than the 62 on oral treatment (264 ± 18 vs 364 ± 16 nmol Pi · mg protein–1· h–1, p 〈 0.001) but similar to that of Type I diabetic patients. Among the Type II diabetic patients, stepwise regression analysis showed that fasting C-peptide level was the only factor independently correlated with Na/K ATPase activity; it explained 23 % of its variance. In fact, in the insulin-treated patients, those with almost total endogenous insulin deficiency (C-peptide 〈 0.2 nmol · l–1) had the lower Na/K ATPase activity (181 ± 21 vs 334 ± 17 nmol Pi · mg protein–1· h–1, p 〈 0.0001). The biological effects of treatment with C-peptide have recently led to the suggestion that this peptide could have a physiological role through the same signalling pathway as insulin, involving G-protein and calcium phosphatase and thus restoring Na/K ATPase activity. The relationship we describe between endogenous C-peptide and this activity is a strong argument for this physiological role. [Diabetologia (1998) 41: 1080–1084]
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1432-0428
    Keywords: Membrane ; fluorescence polarization ; erythrocytes ; diabetes ; insulin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Filtrability of erythrocytes obtained from uncontrolled Type 1 (insulin-dependent) diabetic patients is abnormal, but is corrected by insulin added in vivo or in vitro. As erythrocyte filtrability depends on several determinants, we chose to study a membrane property of erythrocytes from diabetic subjects. Membrane fluidity was studied by fluorescence polarization using a lipophilic probe, the diphenyl-hexatriene and the Coulter Epics V together with a laser Spectra-physics 2000. Fluorescence polarization values obtained for 31 normal subjects (0.253 ± 0.043 SD) and 31 uncontrolled Type 1 diabetic patients (0.231 ± 0.043 SD) were significantly different (p 〈 0.01). Insulin (2.5.10−9 mol/l) added in vitro increased the fluorescence polarization values of red cell membranes from diabetic patients (without insulin, fluorescence polarization values = 0.210 ± 0.032 SD; with insulin, fluorescence polarization values = 0.253 ± 0.024 SD, p 〈 0.001, n =15), but had no effect on normal membranes (without insulin fluorescence polarization values = 0.255 ± 0.037 SD, with insulin, fluorescence polarization values = 0.251 ± 0.026 SD; n =12). Given a relationship between the lipid bilayer and membrane cytoskeleton proteins, this insulin-correctable abnormality of erythrocyte membrane fluidity may be an important determinant of the theological behaviour of erythrocytes from diabetic patients.
    Type of Medium: Electronic Resource
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