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  • 1
    ISSN: 1432-0428
    Keywords: Dog ; insulin therapy ; mathematical model ; soluble insulin ; depot insulin ; absorption ; subcutaneous
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The appearance rate of insulin (calculated insulin secretion rate) in the circulating blood after subcutaneous injection was estimated in diabetic dogs from serial measurements of immunoreactive insulin concentrations using a simple mathematical model based on the insulin half-life and the distribution space. In the case of highly purified monocomponent porcine insulin, maximum concentrations occurred after 30–60 min. The duration of insulin appearance was dose-dependent and the rate of appearance could be described by a bi-exponential function. It was linearly dose-dependent but the effect on glycaemia showed saturation kinetics. The action of the injected dose on the fasting glycaemia diminished when the appearance rate became 〈0.3 mU · kg-1 · min-1. Fractional dose recovery was between 70% and 90% and was not different between depot and regular insulin. Appearance kinetics were not significantly affected by the initial glycaemia. The model presented provides a means for quantitative characterization of different insulin preparations.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0428
    Keywords: Alanine metabolism ; insulin-dependent diabetes ; dog ; isotopic study ; portal insulin infusion ; artificial B cell
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The in vivo flux rates of glucose (6-3H-glucose) and of alanine (U-14C-alanine) were measured in insulin-dependent chronically diabetic dogs which were infused with insulin employing a bedside-type artificial B cell and either the peripheral or the portal venous route. In comparison with non-diabetic control animals the diabetic dogs had near-normal patterns of glucose metabolism and pancreatic glucagon regardless of the route of insulin administration. They also showed reduced basal portal but moderately elevated peripheral insulin levels on peripheral and near-normal peripheral values on portal insulin infusion. Both concentration and production rates of alanine were reduced on peripheral (0.142±0.016mmol/l, 4.73±0.49 μmol·kg−1·min−1, p〈 0.05) but normal on portal insulin (0.206±0.030 mmol/l, 6.33±0.63 μmol·kg−1 ·min−1). The alanine clearance was slightly elevated or normal in the diabetic dogs, and the glucose production from alanine showed a strongly delayed response to an exogenous glucose load on either route of insulin administration. It is concluded that the peripheral hyperinsulinism during posthepatic insulin administration stimulates glucose utilisation to a normal extent, but inhibits the provision of amino groups in resting muscle. Alanine synthesis is thereby reduced, and the carbon moieties are shunted from glucose into circulating lactate. Long-term studies are needed to elucidate the role of the liver under these conditions.
    Type of Medium: Electronic Resource
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