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  • 1
    Electronic Resource
    Electronic Resource
    Absorption rates of subcutaneously injected insulin in the dog as calculated from the plasma insulin levels by means of a simple mathematical model (1983)
    Springer
    Diabetologia 24 (1983), S. 196-201 
    Details
    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
    URL: http://dx.doi.org/10.1007/BF00250161
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    Paper (German National Licenses)
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  • 2
    Electronic Resource
    Electronic Resource
    A physiological solvent for crystalline insulin (1981)
    Springer
    Diabetologia 21 (1981), S. 51-53 
    Details
    ISSN: 1432-0428
    Keywords: Insulin ; crystal ; dissolution ; bicarbonate ; pH
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Insulin is insoluble in water at physiological pH, but dissolves relatively rapidly in plasma. To quantify the ability of various solutions to dissolve crystalline insulin, a simple assay measuring dissolution time was developed. At pH 7.5 and room temperature, distilled water, 0.154 mol/l NaCl, Ringer's lactate solution, and 5% albumin in 0.154 mol/l NaCl did not dissolve insulin crystals within 30 min. Normal postprandial human plasma and a protein-free cell culture medium dissolved insulin crystals within 3 to 8 min. This ability was inhibited by acid titration of the fluids to a stable pH of 6.30, at which point bicarbonate depletion could be implied. Repletion of bicarbonate did restore the ability of these solutions to dissolve insulin crystals, but back-titration to the initial pH with NaOH did not. The effect of sodium bicarbonate alone was strongly concentration dependent above 23 mmol/l. We suggest that the ability of physiological fluids to dissolve insulin crystals at normal pH depends on their bicarbonate content. The ability to dissolve insulin with a physiological solvent which prevents its raggregation promises to facilitate its use in portable pumping systems.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01789114
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    Paper (German National Licenses)
    Fulltext
  • 3
    Electronic Resource
    Electronic Resource
    A physiological solvent for crystalline insulin (1981)
    Springer
    Diabetologia 20 (1981), S. 51-53 
    Details
    ISSN: 1432-0428
    Keywords: Insulin ; crystal ; dissolution ; bicarbonate ; pH
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Insulin is insoluble in water at physiological pH, but dissolves relatively rapidly in plasma. To quantify the ability of various solutions to dissolve crystalline insulin, a simple assay measuring dissolution time was developed. At pH 7.5 and room temperature, distilled water, 0.154 mol/1 NaCl, Ringer's lactate solution, and 5% albumin in 0.154 mol/1 NaCl did not dissolve insulin crystals within 30 min. Normal postprandial human plasma and a proteinfree cell culture medium dissolved insulin crystals within 3 to 8 min. This ability was inhibited by acid titration of the fluids to a stable pH of 6.30, at which point bicarbonate depletion could be implied. Repletion of bicarbonate did restore the ability of these solutions to dissolve insulin crystals, but back-titration to the initial pH with NaOH did not. The effect of sodium bicarbonate alone was strongly concentration dependent above 23 mmol/1. We suggest that the ability of physiological fluids to dissolve insulin crystals at normal pH depends on their bicarbonate content. The ability to dissolve insulin with a physiological solvent which prevents its reaggregation promises to facilitate its use in portable pumping systems.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00253817
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    Paper (German National Licenses)
    Fulltext
  • 4
    Electronic Resource
    Electronic Resource
    Assessment of an algorithm for the artificial B-cell using the normal insulin-glucose relationship in diabetic dogs and men (1980)
    Springer
    Diabetologia 18 (1980), S. 97-107 
    Details
    ISSN: 1432-0428
    Keywords: Artificial B-cell ; algorithm ; glucose-insulin relationship ; regression analysis ; insulin secretion ; insulin half-life ; human diabetes mellitus ; experimental diabetes mellitus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Insulin secretion rates after glucose loading were calculated from peripheral venous IRI concentrations considering half life and distribution space of exogenous insulin in normal men and dogs. The coefficients of multiple linear regression analysis between insulin secretion rates and plasma glucose (level and order and rate of change) were used as algorithm parameters in glucose-controlled insulin infusions. These were carried out in each dog based on individual estimations before the induction of diabetes but in the diabetic patients based on values derived from a group of normal subjects. Using this formula, nearly normal patterns of glucose and of insulin were observed in diabetic men and dogs under basal conditions and after IV glucose loading but not after meals. This algorithm enables selection of the parameters prospectively. The effect of a parameter combination depends on insulin sensitivity and it should be appropriately adapted. In the diabetic patients there was no predictable influence of the brittle or stable characteristics of the disease nor of insulin antibodies on the glucose curves obtained with glucose controlled insulin infusions.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00290484
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    Paper (German National Licenses)
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  • 5
    Electronic Resource
    Electronic Resource
    Glucose metabolism studied isotopically in diabetic dogs: Effect of restoration of peripheral normoinsulinaemia by the artificial B cell (1983)
    Springer
    Diabetologia 25 (1983), S. 411-417 
    Details
    ISSN: 1432-0428
    Keywords: Diabetic dog ; artificial B cell ; glucose metabolism ; tracer kinetics in vivo ; lactate ; carbon recirculation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Normoglycaemia, peripheral normoinsulinaemia, and normoglucagonaemia were restored acutely in chronically diabetic dogs, using an extracorporal artificial B cell with peripheral venous insulin administration. Glucose metabolism was analysed by a non-steady-state tracer technique with double-labelled glucose (6-3H-and U-14C-glucose), and the incorporation of the 14C label into plasma lactate was determined. In the basal state, glucose turnover rates were not different from those in non-diabetic controls; but recirculation of the glucose-C label through the Cori cycle, and lactate labelling from glucose utilization were decreased. The glycaemic response to an intravenous infusion of non-labelled glucose was distinctly enhanced. This was based on a reduction in the rates of glucose disappearance. Its rates of appearance (total endogenous glucose production) were, however, suppressed to a normal extent by the exogenous glucose. Accordingly carbon recycling was nearly totally suppressed during the glucose infusion as in the controls. It is concluded that metabolic recompensation in these fasting, resting diabetic dogs remained incomplete because the interval of normoinsulinaemia, which obviously applied only to the peripheral circulation, was not long enough.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00282520
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    Paper (German National Licenses)
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