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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: Artificial B cell ; dog ; experimental diabetes ; alanine metabolism ; gluconeogenesis ; tracer study
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The flux rates of plasma glucose and alanine were studied isotopically (6-3H-glucose and U-14C-alanine simultaneously) in resting chronically diabetic dogs during short-term treatment with an artificial B cell where the insulin was infused into a peripheral vein. Despite perfect blood glucose control and normal glucose flux rates, the concentration and rates of appearance and disappearance of alanine were significantly elevated in the diabetic animals before, during and after an exogenous glucose load. The incorporation of the carbon moiety of alanine into circulating glucose was also increased, but diminished to a near-normal extent when exogenous glucose was given. The plasma clearance rates for alanine in the diabetic dogs were normal throughout the study. It is concluded that normal blood glucose control in diabetes does not necessarily mean normalization of the entire metabolic network. On the basis of peripheral hyperinsulinaemia alanine formation from glucose and branched chain amino acids is elevated in muscle. This may explain increased flux of alanine despite normal blood glucose control.
    Type of Medium: Electronic Resource
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  • 3
    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
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  • 4
    ISSN: 1432-0428
    Keywords: Subcutaneous glucose concentration ; wick technique ; enzyme sensor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Employing saline-impregnated cotton threads, an implanted-wick technique was adopted in dogs to obtain specimen from the subcutaneous interstitial compartment in order to estimate its glucose concentration. By measuring the protein, potassium and haemoglobin contents, the centrifuged wick fluid was shown to contain the interstitial concentration of solutes after an equilibration time of approximately 15 min. In normal and in diabetic animals the steady state subcutaneous glucose concentration was almost identical to the circulating glucose level when ranged between 2 and 25 mmol/l. Slow alterations in the circulating glucose profile such as those which appear during an oral glucose tolerance test are closely mirrored by the respective levels in the wick fluid. Fast alterations, however, show deviations. The wick-based glucose levels are well paralleled by the current of Clark type glucose oxidase sensors implanted at the same site. Since, on the basis of in vitro calibrations the sensor outputs have only indicated apparent tissue glucose concentrations of between 70 and 90% of glycaemia, another reference is needed for calibration. Under steady state conditions, the wick method, and on this basis in routine measurements the blood glucose concentration, may be recommended as a reference of implanted sensors which can otherwise not be calibrated in situ.
    Type of Medium: Electronic Resource
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  • 5
    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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  • 6
    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
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    European journal of nutrition 36 (1997), S. 355-355 
    ISSN: 1436-6215
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Medicine
    Type of Medium: Electronic Resource
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