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  • 1
    Electronic Resource
    Electronic Resource
    Effect of a new aldose reductase inhibitor, (E)-3-carboxymethyl-5-[(2E)-methyl-3-phenylpropenylidene]rhodanine (ONO-2235) on peripheral nerve disorders in streptozotocin-diabetic rats (1983)
    Springer
    Diabetologia 24 (1983), S. 290-292 
    Details
    ISSN: 1432-0428
    Keywords: Aldose reductase inhibitor ; streptozotocin-diabetic rats ; sciatic nerve sorbitol ; red cell sorbitol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A new aldose reductase inhibitor, (E)-3-carboxy-methyl-5-[(2E-methyl-3-phenylpropenylidene]rhodanine (ONO-2235) was administered orally to streptozotocin-diabetic rats (60 mg/kg IV) for 14 days and its effect on motor nerve conduction velocity studied. The compound significantly improved motor nerve conduction velocity of diabetic rats at a minimal dose of 10 mg · kg-1 · day-1 (treated 28.8±0.5 versus untreated 23.2±4.7 m/s, p 〈 0.01). The sorbitol content of the sciatic nerve and red blood cells measured after 2 weeks was concomitantly reduced in ONO-2235-treated rats (sciatic nerve: 120±13 versus 595±146 nmol/g wet weight; red blood cell: 91±21 versus 165±39 nmol/g haemoglobin; p 〈 0.01 in both 20 mg · kg-1 · day-1-treated versus untreated animals). These results suggest that sorbitol accumulation might contribute to the development of peripheral nerve dysfunction in acutely diabetic animals and the new aldose reductase inhibitor could be a potential drug for therapy of diabetic neuropathy.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00282716
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  • 2
    Electronic Resource
    Electronic Resource
    Glucose enhances type IV collagen production in cultured rat glomerular mesangial cells (1991)
    Springer
    Diabetologia 34 (1991), S. 198-200 
    Details
    ISSN: 1432-0428
    Keywords: Glomerular mesangial cells ; type IV collagen ; effects of high glucose ; mesangial expansion ; diabetic nephropathy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Type IV collagen production by cultured glomerular mesangial cells and the effect of glucose on it were evaluated in order to explore the possible contribution of mesangial cells to the accumulation of type IV collagen in mesangial matrix typically seen in diabetes. Type IV collagen was measured quantitatively by enzyme-linked immunosorbent assay. The majority of type IV collagen was secreted into culture media and secreted-type IV collagen increased with cell growth in early log phase and decreased in late log phase and after confluency. By exposing the cells to high concentrations of glucose (27.8 mmol/l), both secreted- and cell-associated-type IV collagens increased significantly compared with the cells cultured under normal glucose concentrations (5.6 mmol/l) or under equivalent concentrations of mannitol, resulting in a significant increase in total type IV collagen accumulation from 32.1±6.4 (under 5.6 mmol/l glucose) to 51.0±4.6 μg/dish (mean ± SD, n=4) on day 4, from 113.6±6.6 to 156.8±7.1 on day 6, from 248.5±15.2 to 310.0±12.6 on day 8 and from 372.4±14.8 to 507.9±17.2 on day 12. These results indicate the importance of glucose-induced alteration of mesangial cell function in the development of diabetic mesangial expansion.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00418276
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  • 3
    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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  • 4
    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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  • 5
    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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  • 6
    Electronic Resource
    Electronic Resource
    Differential modulation of mitogenic and metabolic actions of insulin-like growth factor I in rat glomerular mesangial cells in high glucose culture (1993)
    Springer
    Diabetologia 36 (1993), S. 276-281 
    Details
    ISSN: 1432-0428
    Keywords: Diabetic nephropathy ; glomerular mesangial cells ; insulin-like growth factor I ; proliferation ; amino acid uptake ; mesangial expansion ; effect of glucose
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In order to explore the possible contribution of insulin-like growth factor I to the development of diabetic nephropathy, the effect of glucose on the mitogenic and metabolic actions of insulin-like growth factor I in cultured rat glomerular mesangial cells was examined. The stimulation of [3H]-thymidine incorporation by insulin-like growth factor I in the cells exposed to high concentrations (55 mmol/l) of glucose (4.6±1.3 fold stimulation) was significantly suppressed as compared with that in the cells cultured in 11 mmol/l glucose (17.5±0.8 fold). In contrast, [3H]-aminoisobutylic acid uptake into the mesangial cells was significantly enhanced by glucose (2.03±0.03 nmol · mg protein−1 · 15 min−1 at 55 mmol/l glucose vs 0.59±0.01 at 11 mmol/l glucose), while 2-deoxyglucose uptake remained unchanged. [125I]-insulin-like growth factor I binding was slightly but significantly increased in the cells exposed to high concentrations of glucose. Thus, glucose may modulate the mitogenic and metabolic actions of insulin-like growth factor I differently in cultured mesangial cells probably at the post-insulin-like growth factor I receptor level. These results may indicate that the differential modulation of the actions of insulin-like growth factor I by glucose could result in the increase in amino acid uptake and decrease in the cell proliferation in the mesangial cells, possibly leading to enhanced mesangial matrix synthesis with a relatively small increase in mesangial cell volume as seen in diabetic nephropathy.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00400228
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  • 7
    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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  • 8
    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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  • 9
    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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  • 10
    Electronic Resource
    Electronic Resource
    Translocation of protein kinase C α and ζ in rat glomerular mesangial cells cultured under high glucose conditions (1994)
    Springer
    Diabetologia 37 (1994), S. 838-841 
    Details
    ISSN: 1432-0428
    Keywords: Key words Diabetic nephropathy, glomerular mesangial cells, protein kinase C, isoenzymes, high glucose.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The activities and expression of protein kinase C isoenzymes were examined in glomerular mesangial cells cultured under high glucose conditions. Exposure of cells to high glucose concentrations (27.8 mmol/l) for more than 3 days resulted in a significant elevation of protein kinase C activities in the membrane fraction. Of the protein kinase C isoenzymes, the levels of protein kinase C α significantly increased in the membrane fraction after 3 days of exposure to glucose, and protein kinase C ζ increased after 5 days of exposure. Levels of protein kinase C δ and ɛ remained unchanged and protein kinase C β and γ were not detected. These results indicate that protein kinase C α and ζ are translocated under high glucose conditions possibly through different mechanisms. [Diabetologia (1994) 37: 838–841]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00404342
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