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  • 1
    ISSN: 1432-0428
    Keywords: Insulin ; insulin receptors ; insulin degradation ; human adipocytes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 125I-insulin binding and receptor-mediated insulin degradation were studied in isolated human fat cells from subcutaneous tissue. A high albumin concentration during cell isolation and incubation protected the fragile human adipocyte from lysis. Binding of tracer was pH dependent with an optimum between 7.4 and 7.6. At 37 °C steady state was reached by 45 min and maintained for at least 2 h. The binding of labelled insulin in the presence of 10 μmol/l unlabelled insulin was only 1–4% of the total insulin binding. The half-maximal displacement of tracer iodoinsulin (10 pmol/l) by unlabelled insulin occurred at 0.25 nmol/l. Kinetic studies of the dissociation of labelled iodoinsulin from fat cells showed a slight acceleration in the presence of a high concentration of unlabelled insulin in the washout buffer as compared to a buffer containing no insulin. At steady state binding about 95% of the cell-associated radioactivity was extracted as iodoinsulin as judged by gel filtration. The remaining 5% co-eluted with iodotyrosine. During 60 min about 90% of the cell-associated radioactivity dissociated as iodoinsulin and the rest as iodotyrosine. Conclusions: 1) A high albumin content of buffers prevents traumatization of the human adipocyte; 2) under these conditions steady state binding of insulin is readily measured at 37 °C; 3) the use of a washing procedure makes the non-specific binding negligible; 4) the human adipocyte insulin receptor has a very high affinity; 5) receptor-mediated insulin degradation is minimal.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 320 (1982), S. 63-66 
    ISSN: 1432-1912
    Keywords: β-Adrenoceptor antagonists ; Intrinsic sympathomimetic activity ; Glucose tolerance test ; Insulin ; Glucose
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effect of β-adrenoceptor antagonists on the intravenous glucose tolerance test was investigated in conscious dogs. dl-Celiprolol (cardioselective with ISA=intrinsic sympathomimetic activity) 200 and 1000 μg/kg i.v., dl-metoprolol (cardio-selective without ISA) 200 and 1000 μg/kg i.v., dl-pindolol (non-selective with ISA) 5 and 25 μg i.v. and l-bupranolol (non-selective without ISA) 10 and 50 μg/kg i.v. were used in the study. The influence of β-adrenoceptor antagonists on the plasma glucose and immunoreactive insulin following the intravenous glucose tolerance test were evaluated by calculating the respective areas under the plasma curve. The present investigtion clearly demonstrates the marked difference between the various β-adrenoceptor antagonists on heart rate and, especially on metabolic parameters. dl-Metoprolol, a β-adrenoceptor antagonist with cardioselectivity and without ISA can be assumed not to alter plasma insulin level and glucose assimilation. l-Bupranolol, a non-selective β-adrenoceptor antagonist without ISA reduces plasma insulin level and probably enhances peripheral glucose uptake, resulting in an “unchanged” glucose tolerance. dl-Celiprolol or dl-pindolol, β-adrenoceptor antagonists with ISA, but cardioselective or non-selective enhance both, basal insulin level and insulin level after glucose stimulation but must be assumed to decrease peripheral glucose uptake since here too glucose tolerance was unchanged.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-1912
    Keywords: β-Adrenoceptor antagonists ; (+)- and (−)-Configuration ; Membrane stabilizing activity ; Glucose tolerance test ; Insulin ; Glucose ; Insulin-glucagon ration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The relevance of the steric configuration to the effects of two non-selective β-adrenoceptor antagonists without intrinsic sympathomimetic activity (+)- and (−)-bupranolol (10 and 50 μg/kg i.v.) and (+)- and (−)-propranolol (100 and 500 μg/kg i.v.) on the i.v. glucose tolerance test (IVGTT) were investigated in conscious, normoglycemic dogs. The effects of the β-adrenoceptor antagonists on plasma glucose, and insulin levels and insulin-glucagon ratio following IVGTT were evaluated by calculating the respective areas under the curve (AUC). The AUC values for plasma glucose were significantly increased by the (−)-configuration of both β-adrenoceptor antagonists. In the (+)-configuration only propranolol (500 μg/kg i.v.) increased the AUC value for plasma glucose significantly. The AUC values for plasma insulin and also for the plasma insulinglucagon ratio were significantly decreased by (−)-propranolol (500 μg/kg i.v.) and by (−)-bupranolol (10 and 50 μg/kg i.v.). Thus the impairment of glucose tolerance, due to suppression of the plasma insulin level, depends mainly on the β-adrenoceptor antagonistic activity of the (−)-configuration.
    Type of Medium: Electronic Resource
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