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  • 1
    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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  • 2
    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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  • 3
    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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  • 4
    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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  • 5
    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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  • 6
    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: 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 ε 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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00404342
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  • 7
    Electronic Resource
    Electronic Resource
    Prevention of glomerular hyperfiltration in rats with streptozotocin-induced diabetes by an atrial natriuretic peptide receptor antagonist (1995)
    Springer
    Diabetologia 38 (1995), S. 536-542 
    Details
    ISSN: 1432-0428
    Keywords: Diabetic nephropathy ; atrial natriuretic peptide ; atrial natriuretic peptide receptor antagonist ; glomerular hyperfiltration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The contribution of atrial natriuretic peptide (ANP) to the development of glomerular hyperfiltration in diabetes was investigated by examining the effects of HS-142-1, a non-peptide antagonist of biological receptors for ANP, on glomerular filtration rate (GFR) and renal plasma flow (RPF) in rats with streptozotocin-induced diabetes. Three to four weeks after streptozotocin injection, the plasma concentration of ANP, urinary cyclic GMP excretion rate, GFR, and RPF were significantly higher in diabetic rats than in control rats. The increase in GFR and RPF in diabetic rats was significantly reduced, in a dose-dependent manner, by a single intravenous injection of HS-142-1; the maximal effect was apparent at a dose of 10 mg per kg of body weight. Continuous subcutaneous administration of HS-142-1 with an osmotic minipump for 3 to 4 weeks, beginning 2 days after streptozotocin injection, prevented the increases in urinary cyclic GMP excretion rate, GFR, and RPF observed in untreated diabetic rats. These results highlight the importance of ANP in the development of diabetic glomerular hyperfiltration and indicate that this condition can be prevented by continuous inhibition of the action of ANP.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00400721
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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
    Current status of Type 2 (non-insulin-dependent) diabetic subjects on dialysis therapy in Japan (1993)
    Springer
    Diabetologia 36 (1993), S. 1105-1108 
    Details
    ISSN: 1432-0428
    Keywords: Type 2 (non-insulin-dependent) diabetes mellitus ; end-stage renal disease ; dialysis ; neuropathy ; mortality ; Japan ; chronic glomerulonephritis ; vasculopathy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary According to a national survey of dialysis patients in Japan conducted by the Japanese Society for Dialysis Therapy, there were 1,033 patients on dialysis in the Shiga area which has a population of about 1.2 million. Of these 1,033 dialysis patients 140 were the result of diabetic nephropathy. From four hospitals affiliated to Shiga University of Medical Science the medical records of 90 diabetic subjects on dialysis therapy were reviewed and various clinical parameters were analysed and compared with those of patients with chronic glomerulonephritis. Since only one patient had Type 1 (insulin-dependent) diabetes, the remaining 89 with Type 2 (non-insulin-dependent) diabetes were used for this study. The significantly different variables between patients with Type 2 diabetes and chronic glomerulonephritis were age (60.4 vs 54.6 years,p〈0.05), BMI (22.4 vs 20.6 kg/m2,p〈0.001), cardiothoracic ratio (56.4 vs 53.3%,p〈0.001), mean blood pressure (110 vs 117 mm Hg,p〈0.05), serum creatinine (9.0 vs 11.5 mg/dl,p〈0.001), serum urea-N (98.2 vs 115.5 mg/dl,p〈0.001), serum total protein (6.0 vs 6.5 g/dl,p〈0.001) and serum albumin (3.5 vs. 3.9 g/dl,p〈0.001). Serum levels of cholesterol and triglyceride were not significantly different between two groups, though the prevalence of electrocardiogram abnormalities, oedema, neuropathy, myocardial infarction and cerebrovascular diseases was significantly higher in the Type 2 diabetic group. These results suggested that Type 2 diabetic patients with end-stage renal disease were older, more malnurished, fluid overloaded and multi-morbid as a result of vasculopathy and neuropathy. However, the analysis of causes of death in Type 2 diabetic patients (n=24) and patients with chronic glomerulonephritis (n=26) failed to provide evidence of higher risk of cardiac death in the Type 2 diabetic group compared to the group with chronic glomerulonephritis (37.5 vs 34.6%, NS). In the Type 2 diabetic patients on dialysis therapy, malnutrition, fluid overload and neuropathy appeared to be significant factors influencing the outcome of the therapy, while in patients with chronic glomerulonephritis, age and vascular morbidities were considered to be major risk factors for the prognosis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02374506
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  • 10
    Electronic Resource
    Electronic Resource
    Prevention of glomerular hyperfiltration in rats with streptozotocin-induced diabetes by an atrial natriuretic peptide receptor antagonist (1995)
    Springer
    Diabetologia 38 (1995), S. 536-542 
    Details
    ISSN: 1432-0428
    Keywords: Key words Diabetic nephropathy ; atrial natriuretic peptide ; atrial natriuretic peptide receptor antagonist ; glomerular hyperfiltration.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The contribution of atrial natriuretic peptide (ANP) to the development of glomerular hyperfiltration in diabetes was investigated by examining the effects of HS-142-1, a non-peptide antagonist of biological receptors for ANP, on glomerular filtration rate (GFR) and renal plasma flow (RPF) in rats with streptozotocin-induced diabetes. Three to four weeks after streptozotocin injection, the plasma concentration of ANP, urinary cyclic GMP excretion rate, GFR, and RPF were significantly higher in diabetic rats than in control rats. The increase in GFR and RPF in diabetic rats was significantly reduced, in a dose-dependent manner, by a single intravenous injection of HS-142-1; the maximal effect was apparent at a dose of 10 mg per kg of body weight. Continuous subcutaneous administration of HS-142-1 with an osmotic minipump for 3 to 4 weeks, beginning 2 days after streptozotocin injection, prevented the increases in urinary cyclic GMP excretion rate, GFR, and RPF observed in untreated diabetic rats. These results highlight the importance of ANP in the development of diabetic glomerular hyperfiltration and indicate that this condition can be prevented by continuous inhibition of the action of ANP. [Diabetologia (1995) 38: 536–542]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00400721
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