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  • 1
    Electronic Resource
    Electronic Resource
    Effect of insulin on the synthesis and release of lipid peroxide by cultured hepatocytes isolated from normal and diabetic rats (1984)
    Springer
    Cellular and molecular life sciences 40 (1984), S. 394-396 
    Details
    ISSN: 1420-9071
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Lipid peroxide content in hepatocytes isolated from ketotic diabetic rats was higher than normal, and the release of peroxide into the media was also elevated for the initial 18 h. Insulin suppressed both peroxide release and synthesis by cultured hepatocytes isolated from normal and from diabetic rats.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01952571
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    Paper (German National Licenses)
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  • 2
    Electronic Resource
    Electronic Resource
    Abnormal glutathione metabolism and increased cytotoxicity caused by H2O2 in human umbilical vein endothelial cells cultured in high glucose medium (1994)
    Springer
    Diabetologia 37 (1994), S. 264-269 
    Details
    ISSN: 1432-0428
    Keywords: Human umbilical vein endothelial cells ; high glucose ; oxygen radicals ; radical scavenger ; glutathione redox cycle
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary To determine whether increased oxidative stress in diabetes mellitus is due to an impaired freeradical scavenger function in endothelial cells, GSH-dependent H2O2 degradation in human umbilical vein endothelial cells was studied. The GSH-dependent, NaN3-uninhibitable H2O2-degradation in endothelial cells was reduced by 48% (p 〈0.001) when the cells were exposed to 33 mmol/l d-glucose vs 5.5 mmol/l d-glucose. This impairment was dependent not only on the d-glucose concentration in the medium but also on d-glucose specific metabolism, since neither 27.5 mmol/l l-glucose nor 27.5 mmol/l d-raffinose had any effect on the peroxide degradation activity. Activation of the glutathione redox cycle by H2O2 in cells exposed to high glucose concentrations was attenuated as compared with 5.5 mmol/l d-glucose because of: 1) a 42% decrease (p 〈0.001) in intracellular NADPH content, and 2) a 34% reduction (p 〈0.01) in glutathione release into the media. This results in an accumulation of GSSG in the cells following exposure to H2O2. Both H2O2-evoked 51Cr-release and H2O2-induced endothelial cell damage were significantly (p 〈0.01) greater in the 33 mmol/l d-glucose group than in the 5.5 mmol/l d-glucose group. These results indicate that the abnormal glutathione redox cycle observed in endothelial cells is induced by high glucose concentrations in the medium, resulting in an impairment of reduced GSH-dependent H2O2-degradation. These abnormalities may associate with the increased cellular damage following an exogenous exposure to H2O2.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00398053
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    Paper (German National Licenses)
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  • 3
    Electronic Resource
    Electronic Resource
    Oxidized lipoproteins found in patients with NIDDM stimulate radical-induced monocyte chemoattractant protein-1 mRNA expression in cultured human endothelial cells (1997)
    Springer
    Diabetologia 40 (1997), S. 662-670 
    Details
    ISSN: 1432-0428
    Keywords: Keywords Oxidized lipoprotein ; free radical ; atherosclerosis ; endothelial cells ; antioxidants.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Although oxidized low density lipoprotein (LDL) exists in plasma from diabetic patients, there are few studies on its biological activity. Thus, we investigated the biological potency of LDL plus intermediate density lipoprotein fraction isolated from 12 non-diabetic and 24 non-insulin-dependent diabetic subjects of similar age and body mass index, in order to induce monocyte chemoattractant protein-1 (MCP-1) mRNA expression in cultured human endothelial cells. MCP-1 mRNA content in the cells exposed to the lipoproteins isolated from the diabetic patients was significantly higher than that from the control subjects (p 〈 0.001). The increment of MCP-1 mRNA content was positively correlated with not only HbA1 c (r = 0.58, p 〈 0.0001) but also lysophosphatidylcholine (LPC) content in the lipoprotein (r = 0.46, p 〈 0.005) and was negatively correlated with diene formation lag time as a marker of oxidizability of the lipoprotein (r = – 0.33, p 〈 0.05). Treatments of the cells with either 50 μmol/l probucol, 50 μmol/l α-tocopherol, or 0.1 mmol/l deferoxamine suppressed the increase in MCP-1 mRNA content induced by diabetic lipoproteins, respectively. Furthermore, the diabetic lipoproteins activated nuclear transcription factor NF-kB in the cells, which was inhibited by pre-treatment of cells with 50 μmol/l probucol. These data indicate that oxidatively modified lipoproteins found in diabetic plasma stimulate MCP-1 gene expression in endothelial cells. The LPC content which reflects oxidative modification of lipoprotein is at least a possible marker of biological activity to increase an atherogenic cytokine in endothelial cells. [Diabetologia (1997) 40: 662–670]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001250050731
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  • 4
    Electronic Resource
    Electronic Resource
    Usefulness of waveform analysis of popliteal artery in Type II diabetic patients using gated magnetic resonance 2D-cine-PC imaging and 31P spectroscopy (2000)
    Springer
    Diabetologia 43 (2000), S. 1031-1038 
    Details
    ISSN: 1432-0428
    Keywords: Keywords Magnetic resonance ; popliteal artery ; waveform ; flow volume ; occlusive arterial disease ; arterial resistance ; plantar muscle ; high energy phosphate content.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Aims/hypothesis. We studied 76 patients with Type II (non-insulin-dependent) diabetes mellitus and 16 age-matched non-diabetic subjects (control group) to clarify qualitative and quantitative abnormalities of waveform and flow volume of the popliteal artery. Methods. The 76 diabetic patients comprised 16 patients with occlusive arterial disease in the lower extremities [arteriosclerosis obliterans (ASO) group] and 60 patients free from this disease (non-ASO group). We flow analysed the popliteal artery and measured the phosphocreatine to inorganic phosphate ratio of resting plantar muscles to identify risk factors for foot lesions using gated magnetic resonance two-dimensional cine-mode phase-contrast imaging and 31P spectroscopy. Results. The control and non-ASO groups had a triphasic waveform with systolic, early and late diastolic components. All ASO patients had an abnormal monophasic waveform and a lower ankle brachial index than that of the control and non-ASO groups. To clarify the mechanism of reduced flow volume of lower extremities, we assigned the 60 patients of the non-ASO group to the three subgroups based on their levels of total flow volume of the popliteal artery. The lowest group showed an abnormal triphasic waveform with lower amplitudes of systolic and late diastolic components and flow velocities in foot arteries than those of the highest group although ABI was similar. From stepwise multiple regression analysis, late diastolic flow volume was identified as an independent determinant for the phosphocreatine to inorganic phosphate ratio (r 2 = 0.484, p 〈 0.001). Conclusion/interpretation. Waveform analysis of popliteal artery provides a powerful tool for identifying impaired peripheral circulation caused by either occlusive arterial disease or increased arterial resistance in diabetic patients. [Diabetologia (2000) 43: 1031–1038]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001250051486
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  • 5
    Electronic Resource
    Electronic Resource
    Increased intestinal glucose absorption and postprandial hyperglycaemia at the early step of glucose intolerance in Otsuka Long-Evans Tokushima Fatty Rats (1998)
    Springer
    Diabetologia 41 (1998), S. 1459-1466 
    Details
    ISSN: 1432-0428
    Keywords: Keywords OLETF ; xylose ; SGLT1 ; intestinal hypertrophy ; glucose absorption ; postprandial hyperglycaemia.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Otsuka Long-Evans Tokushima Fatty (OLETF) rats are reported to be obese Type II (non-insulin-dependent) diabetic rats with insulin resistance and impaired insulin secretion. To investigate the contribution of intestinal glucose absorption to postprandial hyperglycaemia, we determined the plasma xylose concentrations after an 0.8 g/kg oral xylose load which was used as a test of small intestinal glucose absorption in 6-week-old OLETF rats and weight-matched Long-Evans Tokushima Otsuka (LETO) rats. An oral glucose tolerance test showed that OLETF rats developed hyperglycaemia at 60 and 90 min after the glucose load, though the fasting plasma glucose concentration, insulin concentration and insulin-induced in vivo glucose utilization rate were similar. Consistently, in an oral D-xylose loading test, the peak concentration of plasma xylose in OLETF rats was increased by 58.7 % compared with that of LETO rats (p 〈 0.005). The disappearance rate of plasma xylose concentrations after intravenous xylose loading did not differ between the two strains. Co-treatment with 0.4 g/kg phlorizin, a specific inhibitor of sodium-dependent glucose transporter 1 (SGLT1), abolished both plasma glucose and xylose concentrations after the loads. Morphological studies showed that both the small intestinal wet weight and surface area were 30 % larger in the OLETF rats than in the LETO rats. Furthermore, the SGLT1 mRNA content of OLETF rats also increased compared with LETO rats. These results suggest that an increased SGLT1 expression concomitant with intestinal hypertrophy in OLETF rats is partly associated with postprandial hyperglycaemia before the onset of insulin resistance and hyperinsulinaemia. [Diabetologia (1998) 41: 1459–1466]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001250051092
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  • 6
    Electronic Resource
    Electronic Resource
    1H- and 31P-magnetic resonance spectroscopy and imaging as a new diagnostic tool to evaluate neuropathic foot ulcers in Type II diabetic patients (2000)
    Springer
    Diabetologia 43 (2000), S. 165-172 
    Details
    ISSN: 1432-0428
    Keywords: Keywords Magnetic resonance, spectroscopy, imaging, neuropathic foot ulcers, fat, phosphocreatine, intracellular pH.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Aims/hypothesis. We studied 36 Type II (non-insulin-dependent) diabetic patients without occlusive arterial diseases in the lower extremities and 12 age-matched and sex-matched non-diabetic subjects to clarify the association between diabetic polyneuropathy and foot ulcers using 1H- and 31P-magnetic resonance spectroscopy and imaging.¶Methods. The 36 diabetic patients consisted of 12 patients with superficial foot ulcers and 24 patients free from this disease. We measured fat to water and phosphocreatine to inorganic phosphate (PCr:Pi) ratios and calculated the intracellular pH of resting plantar muscles by depth-resolved surface-coil spectroscopy using an 1H-31P double tuned coil. Furthermore, foot vasculature, fat and PCr contents of plantar muscles were visualised by phase-contrast angiography, T1-weighted spin-echo imaging and 31P-chemical shift imaging.¶Results. The 12 foot ulcer patients showed a reduced PCr to Pi ratio (p 〈 0.001) and peripheral nerve functions (p 〈 0.01–0.001) but an increased fat to water ratio (p 〈 0.001) and intracellular pH (p 〈 0.001) compared with the 24 patients without ulcers. From stepwise multiple regression analyses, motor nerve function as well as severity of nephropathy was associated with both fat to water and PCr to Pi ratios. When these patients were categorised into three groups based on their level of motor nerve function, the frequency of foot ulcers of the lowest group was higher than that of the highest group.¶Conclusion/interpretation. Our findings indicated that motor nerve dysfunction in diabetic patients was closely associated with impaired energy metabolism, fatty infiltration and increased intracellular pH of plantar muscles and high frequency of foot ulcers. These new techniques could contribute to help clarify the predisposing factors for foot ulcers. [Diabetologia (2000) 43: 165–172]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001250050025
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  • 7
    Electronic Resource
    Electronic Resource
    Abnormal glutathione metabolism and increased cytotoxicity caused by H2O2 in human umbilical vein endothelial cells cultured in high glucose medium (1994)
    Springer
    Diabetologia 37 (1994), S. 264-269 
    Details
    ISSN: 1432-0428
    Keywords: Key words Human umbilical vein endothelial cells, high glucose, oxygen radicals, radical scavenger, glutathione redox cycle.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary To determine whether increased oxidative stress in diabetes mellitus is due to an impaired free-radical scavenger function in endothelial cells, GSH-dependent H2O2 degradation in human umbilical vein endothelial cells was studied. The GSH-dependent, NaN3-uninhibitable H2O2-degradation in endothelial cells was reduced by 48 % (p 〈0.001) when the cells were exposed to 33 mmol/l D-glucose vs 5.5 mmol/l D-glucose. This impairment was dependent not only on the D-glucose concentration in the medium but also on D-glucose specific metabolism, since neither 27.5 mmol/l L-glucose nor 27.5 mmol/l D-raffinose had any effect on the peroxide degradation activity. Activation of the glutathione redox cycle by H2O2 in cells exposed to high glucose concentrations was attenuated as compared with 5.5 mmol/l D-glucose because of: 1) a 42 % decrease (p 〈0.001) in intracellular NADPH content, and 2) a 34 % reduction (p 〈0.01) in glutathione release into the media. This results in an accumulation of GSSG in the cells following exposure to H2O2. Both H2O2-evoked 51Cr-release and H2O2-induced endothelial cell damage were significantly (p 〈0.01) greater in the 33 mmol/l D-glucose group than in the 5.5 mmol/l D-glucose group. These results indicate that the abnormal glutathione redox cycle observed in endothelial cells is induced by high glucose concentrations in the medium, resulting in an impairment of reduced GSH-dependent H2O2degradation. These abnormalities may associate with the increased cellular damage following an exogenous exposure to H2O2. [Diabetologia (1994) 37: 264–269]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00398053
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  • 8
    Electronic Resource
    Electronic Resource
    A new antidiabetic agent (JTT-501) rapidly stimulates glucose disposal rates by enhancing insulin signal transduction in skeletal muscle (1999)
    Springer
    Diabetologia 42 (1999), S. 151-159 
    Details
    ISSN: 1432-0428
    Keywords: Keywords Euglycaemic insulin clamp ; insulin sensitizer ; isoxazolidinedione ; insulin signaling ; JTT-501
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A newly synthesized antidiabetic agent, JTT-501 is an isoxazolidinedione rather than a thiazolidinedione. An oral dose of JTT-501 (100 mg · kg–1· day–1) given to 12-week-old male Zucker fatty rats for 7 days led to the amelioration of both hyperinsulinaemia (40 % of non-treated) and hypertriglyceridaemia (23 % of non-treated) as well as a 2.4-fold increased insulin sensitivity as determined by a euglycaemic insulin clamp. In our study, we further evaluated the acute effect of JTT-501 on both the glucose infusion rates (GIR) and insulin signalling in skeletal muscle. Male Sprague-Dawley (SD) rats aged 10 weeks were injected intravenously with JTT-501 (5 mg/kg) and then a euglycaemic insulin clamp was initiated and glucose infusion rates monitored for 150 min. We found that this treatment increased the glucose infusion rate by 33 % during the last 30 min in SD rats. After the clamp had been initiated for 30 min, the insulin-stimulated phosphatidylinositol 3-kinase (PI3-kinase) activities co-immunoprecipitated with insulin receptor substrate 1 (IRS-1) were also enhanced, resulting in increased glycogen synthase activities in the soleus muscles. Treatment with JTT-501 also enhanced the phosphorylation of insulin receptors and insulin receptor-substrate 1 rapidly as well as the phosphatidylinositol 3-kinase activities, which were stimulated by a bolus injection of insulin. Similarly, JTT-501 stimulated the glucose infusion rate by 30 % and enhanced insulin signalling in Zucker fatty rats. In conclusion, a newly developed isoxazolidinedione, JTT-501, rapidly potentiates the insulin sensitivity of skeletal muscle by enhancing insulin signalling and could be useful for the treatment of insulin-resistant diabetic subjects. [Diabetologia (1999) 42: 151–159]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001250051133
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  • 9
    Electronic Resource
    Electronic Resource
    Increased plasma post-heparin diamine oxidase activity and plant sterol levels in streptozotocin diabetic rat
    Amsterdam : Elsevier
    Biochemical and Biophysical Research Communications 186 (1992), S. 398-404 
    Details
    ISSN: 0006-291X
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Chemistry and Pharmacology , Physics
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1016/S0006-291X(05)80821-6
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  • 10
    Electronic Resource
    Electronic Resource
    Increased plasma post-heparin diamine oxidase activity and plant sterol levels in streptozotocin diabetic rat
    Amsterdam : Elsevier
    Biochemical and Biophysical Research Communications 186 (1992), S. 398-404 
    Details
    ISSN: 0006-291X
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Chemistry and Pharmacology , Physics
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1016/S0006-291X(05)80821-6
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    Paper (German National Licenses)
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