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  • 1
    Electronic Resource
    Electronic Resource
    Effects of metformin on insulin receptor tyrosine kinase activity in rat adipocytes (1986)
    Springer
    Diabetologia 29 (1986), S. 798-801 
    Details
    ISSN: 1432-0428
    Keywords: Insulin receptor ; Tyrosine kinase activity ; Intact cell phosphorylation ; Metformin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The cellular mechanism(s) by which the biguanide, metformin, exerts its antihyperglycaemic effect was investigated. Rat adipocytes were either treated acutely (2 h) or maintained in a biochemically defined medium (20 h) in the presence or absence of metformin (1 x 10−4 mol/1). Exposure to the drug resulted in a significant enhancement (p 〈 0.01) of hexose transport in both the absence (basal) and presence of insulin. Stimulation of transport was not explained by the increase in the basal state alone, since the incremental response to maximally effective concentrations of insulin was significantly enhancedp〈0.025. Insulin-receptor tyrosine kinase activity was examined under the same experimental conditions. Activity of the kinase was unaltered as evaluated by phosphorylation of an artificial substrate and by phosphorylation of the receptor in situ. Furthermore, in this investigation neither insulin receptor number nor affinity was changed in adipose tissue treated with metformin. These studies indicate that metformin potentiates the effect of insulin on glucose transport at a site(s) beyond insulin receptor binding and phosphorylation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00873219
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    Paper (German National Licenses)
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  • 2
    Electronic Resource
    Electronic Resource
    A phase I–II study of 9-cis retinoic acid and interferon-α2b in patients with advanced renal-cell carcinoma: An NCIC Clinical Trials Group study (2000)
    Springer
    Annals of oncology 11 (2000), S. 1387-1389 
    Details
    ISSN: 1569-8041
    Keywords: interferon-α ; pharmacokinetics ; renal carcinoma ; retinoids
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Although advanced renal-cell carcinoma (RCC) responds poorly to standardtherapies, phase I–II trials have shown activity for combinations ofinterferon-α2b (IFN) with a retinoid. Alitretinoin (9-cis RA) isan endogenous retinoid with high binding affinity for both RAR and RXRreceptor families. This phase I–II study enrolled 38 patients with RCCin a dose-escalation study of tolerability, pharmacokinetics (PK), andefficacy of twice daily oral 9-cis RA with subcutaneous IFN. Incontrast to studies with similar doses of daily 9-cis RA, PK studiesfound a consistent reduction in 9-cis RA concentrations of about50% after multiple b.i.d. doses of 30 or 50 mg/m2,independent of cotreatment with IFN. In the phase I portion, toxicitiesincluded systemic symptoms typical of IFN and biochemical abnormalitiespreviously associated with retinoids. Two patients experienced dose-limitingtoxicity at 50 mg/m2 b.i.d. of 9-cis RA, thus therecommended phase II dose was 30 mg/m2 b.i.d. One of twenty-sixevaluable patients achieved a durable objective partial remission, andrepeated dosing with this regimen was poorly tolerated. This combination ofretinoid and interferon is not recommended for further study in RCC.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1026579400806
    Library Location Call Number Volume/Issue/Year Availability
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    Paper (German National Licenses)
    Fulltext
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