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  • 1
    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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  • 2
    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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    Paper (German National Licenses)
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  • 3
    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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    Paper (German National Licenses)
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