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  • 1
    ISSN: 1432-0428
    Keywords: Chemically-modified insulins ; insulin structure-function ; bioactivity and metabolism in vivo ; competitive antagonism ; hypoglycaemia ; non-esterified fatty acids
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The biological properties of three covalently-linked insulin dimers were studied in greyhounds. Constant infusions showed that the plasma distribution kinetics were slower for the dimers than for insulin. The metabolic clearance rates of the three dimers (10.3±0.4, 8.8±0.5, 8.2±0.5 ml· min-1· kg-1; mean ± SEM) were significantly lower than that of insulin (19±0.8 ml · min-1 · kg-1), and their hypoglycaemic effects (11.2%, 3% and 0.3%) were markedly reduced compared with their lipogenic potencies in vitro (80%, 30% and 13%, respectively). A low dose infusion of insulin or an equipotent dose of one of the dimers significantly prolonged the effects of an insulin bolus on plasma glucose but not on non-esterified fatty acids. The apparent distribution space (106.4±11.9 ml/kg) and clearance rate (14.7±0.5 ml · min-1 · kg-1) of an insulin bolus were significantly reduced by one dimer (44.5±8.4 ml/ kg and 10.7±2.8ml·min-1·kg-1) but not by the equipotent insulin infusion (102.7±8.2ml/kg and 16.4±0.07ml· min-1 · kg-1). The apparent partial competitive antagonism of insulin by the dimers that has been reported in vitro can be observed in vivo, in that antagonism of insulin metabolism was directly demonstrated with one of the dimers.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-1041
    Keywords: propranolol ; practolol ; betaxolol ; hypoglycaemia ; free fatty acids ; glycerol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary 1. Six healthy male volunteers received equivalent intravenous beta-blocking doses of propranolol, practolol and betaxolol (SL75212) or saline at weekly intervals Sixty minutes later 0.1 unit/kg insulin was given intravenously. 2. In all studies, maximum hypoglycaemia (mean 1.2 mmol/l) was reached thirty minutes after insulin. Recovery from hypoglycaemia was delayed with propranolol but practolol and betaxolol had no effect. 3. Propranolol blocked the tachycardia and widening of pulse pressure seen in saline treated subjects. It also blocked the rebound rise in free fatty acids (FFA) and glycerol concentrations that followed the nadir of hypoglycaemia. 4. Neither practolol nor betaxolol had significant effects on pulse rate or blood pressure but betaxolol resembled propranolol in blocking the rebound rise in FFA and glycerol, while practolol blocked the rise in glycerol alone. 5. The magnitude of the rise in growth hormone following hypoglycaemia was similar in all groups, but the peak was earlier after practolol and betaxolol.
    Type of Medium: Electronic Resource
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