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  • 1
    Electronic Resource
    Electronic Resource
    The metabolic and hormonal responses to glucose infusion in anaesthetized normal and diabetic dogs controlled by an artificial B-cell (1980)
    Springer
    Diabetologia 18 (1980), S. 479-485 
    Details
    ISSN: 1432-0428
    Keywords: Glucose ; artificial pancreas ; insulin ; glucagon ; lactate ; pyruvate ; alanine ; free fatty acids ; anaesthesia ; metabolic response ; insulin infusion ; diabetes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The metabolic response to glucose infusion in anaesthetized normal and pancreatectomized dogs has been assessed. Normoglycaemia was achieved in the diabetic dogs with an external artificial B-cell which administered insulin into the peripheral circulation. No differences were found in the levels of blood glucose, glucagon, lactate, pyruvate and plasma non-esterified fatty acids, either in the fasting state or in response to glucose infusion. However, compared to normal animals normoglycaemic diabetic dogs had significantly elevated circulating levels of insulin and alanine at all times. Fasting levels of the same hormones and metabolites were also measured in conscious dogs. Blood pyruvate levels were higher, and plasma non-esterified fatty acid levels lower, in the anaesthetized animals. There were also minor but consistent changes in blood glucose and plasma insulin while glucagon, lactate and alanine levels were unaffected by anaesthesia. In conclusion, controlled barbiturate anaesthesia has relatively minor effects on the metabolic and hormonal status of the dog. The metabolic and hormonal response to glucose infusion in pancreatectomized dogs treated with an artificial B-cell was almost entirely normalized, except for peripheral hyperinsulinaemia and hyperalaninaemia.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00261704
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  • 2
    Electronic Resource
    Electronic Resource
    Blood glucose control and insulin clearance in unrestrained diabetic dogs portally infused with a portable insulin delivery system (1980)
    Springer
    Diabetologia 19 (1980), S. 452-457 
    Details
    ISSN: 1432-0428
    Keywords: Glucose ; insulin ; infusion ; hepatic degradation ; insulin clearance ; portal
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Long term glucose control in pancreatectomised dogs has been obtained with portal insulin therapy. When compared to a previous similar study using peripheral infusions, 20% less exogenous insulin was required and peripheral fasting insulin levels were 30% lower. Animals (n = 5) were unrestrained, conscious and carried a programmable insulin pump for 163–224 days. In the post-absorptive state blood glucose was normal (87±5 mg/dl) as was plasma insulin (10±1 mU/l) with porcine insulin infused at a basal rate of 0.36±0.01 mU/kg/min. Following ingestion of a standard mixed meal the infusion rate was increased to 2.47±0.09 mU/kg/ min for 7 1/2 h resulting in post-prandial normalisation of blood glucose. Peripheral plasma insulin levels were twice normal during the post-prandial infusion, but only half those previously reported with peripheral infusions. Insulin clearance rates were 37 ml/kg/min in the basal state and rose significantly post-prandially. In the absence of extra meal-time insulin the clearance rate was unaffected by the resulting post-prandial hyperglycaemia and similar to values observed with insulin infused peripherally at 0.45±0.03 mU/kg/min. No significant increase in the post-prandial rate of insulin clearance relative to the fasting rate was observed with peripherally administered insulin. It was thus concluded that portal insulin replacement in pancreatectomised dogs could normalise both blood glucose and insulin in the fasting state, but post-prandial peripheral insulin levels remained elevated.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00281825
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  • 3
    Electronic Resource
    Electronic Resource
    Pancreatic transplantation and the artificial pancreas (1982)
    Springer
    Diabetologia 22 (1982), S. 299-299 
    Details
    ISSN: 1432-0428
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00281313
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  • 4
    Electronic Resource
    Electronic Resource
    Blood glucose regulation using closed- and open-loop insulin delivery systems (1979)
    Springer
    Diabetologia 17 (1979), S. 45-49 
    Details
    ISSN: 1432-0428
    Keywords: Blood glucose regulation and control ; glucose infusion ; continuous low dose peripheral insulin infusion ; pancreatectomized dogs ; artificial beta cell ; hyperinsulinaemia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Glucose was infused into anaesthetized dogs before and after pancreatectomy. In the diabetics blood glucose was regulated first by closed-loop and then by open-loop insulin delivery schemes. Insulin requirements for the latter were determined by resolving the former into a sequence of 3 different infusion rates: during the baseline and recovery periods, basal insulin was delivered at 0.37±0.02 mU/kg/min, while during the 60 min glucose infusion (10 mg/kg/min) there was an 8 min infusion at 4.96±0.37 mU/kg/min and a 52 min component at 1.85±0.08 mU/kg/min. With the open-loop method under these highly standardized conditions glycaemia was similar to normal controls but IRI levels were significantly higher, 13.5 vs 8.0 μU/ml (p〈0.05) in the baseline and recovery periods and 74 vs 25 μU/ml (p〈0.05) during the glucose infusion. It was concluded that: constant normogly-caemia can be maintained in the basal state by a constant rate of peripheral insulin delivery but at rates resulting in peripheral hyperinsulinaemia; the glycaemic response to glucose infusion can be normalized by a two component waveform of insulin delivery; and the closed-loop method can serve as a useful guide in determining insulin requirements.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01222977
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  • 5
    Electronic Resource
    Electronic Resource
    Blood glucose regulation using an open-loop insulin delivery system in pancreatectomized dogs given glucose infusions (1979)
    Springer
    Diabetologia 16 (1979), S. 129-133 
    Details
    ISSN: 1432-0428
    Keywords: Blood glucose regulation and control ; glucose infusion ; continuous low dose portal insulin infusion ; pancreatectomized dog ; artificial beta cell ; hyperinsulinaemia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary This study characterizes the glycaemic and insulin responses of a group of 5 anaesthetized dogs to a portal glucose infusion of 10 mg/kg/min before and after pancreatectomy. Insulin was administered intraportally to the pancreatectomized dogs according to a simple preprogrammed waveform composed of a constant basal rate of 0.35±0.02 mU/kg/min which was increased to 2.00mU/kg/min at the time of the 60 minute glucose challenge. When this square waveform was applied the glycaemic response was similar to that seen in the normal controls in the baseline and challenge periods. Blood glucose concentration differed significantly (p〈0.05) only from 20 to 100 minutes after the end of the challenge when it was higher by 20±1 mg/dl. Insulin levels were not significantly different from controls. It may be concluded that normoglycaemia and normoinsulinaemia can be maintained by a simple constant rate of portal insulin delivery while the blood glucose response to a glucose infusion can be ostensibly normalized without hyperinsulinaemia simply by enhancing insulin delivery during the challenge. The feasibility of this approach implies that with further development of the preprogrammed waveforms and with a greater understanding of their characteristics portable insulin delivery systems may be realized which accomodate more physiological challenges. The portal route for insulin delivery may however be necessary if peripheral hyperinsulinism is inappropriate.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01225463
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  • 6
    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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  • 7
    Electronic Resource
    Electronic Resource
    Insulin aggregation in artificial delivery systems (1980)
    Springer
    Diabetologia 19 (1980), S. 1-9 
    Details
    ISSN: 1432-0428
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Conclusions Abrupt changes in flow path, motion, elevated temperatures, metal ion contamination, impure insulin formulations, CO2 diffusion, pH drop, dissimilar metal pump components, salt concentration, inappropriate diluents, elevated temperatures, refrigeration temperatures, processing, insulin heterogeneity, and buffering systems have been implicated to a greater or lesser extent in the plugging of insulin delivery devices. Before the rate at which insulin loses its biological activity in delivery systems can be assessed it is obvious that anti-aggregating diluents must be developed and subjected to long-term testing both in vitro and in vivo. Until such stable homogenous formulations are available the knowledge presented in this article will serve to decrease, but not eliminate, the problem of insulin aggregation in delivery systems. Further experiments are in progress and preliminary results [41] provide evidence that the problems cited are not without resolution. In this regard serum apparently contains factor(s) that promote the dissolution of insulin and prevent the formation of peptide aggregates in dilute solutions [41]. Many laboratories are now working to resolve the problem of insulin aggregation in artificial delivery devices.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00258302
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  • 8
    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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  • 9
    Electronic Resource
    Electronic Resource
    Differential binding of sulphated insulin to adipocytes and hepatocytes (1984)
    Springer
    Diabetologia 27 (1984), S. 184-188 
    Details
    ISSN: 1432-0428
    Keywords: Sulphated insulin ; adipocytes ; hepatocytes ; insulin ; receptors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The polymerization and precipitation of highly purified insulins which causes major problems in portable infusion systems does not occur with sulphated insulin. To compare the biological behaviour of sulphated insulin with that of a neutral highly purified monocomponent insulin, insulin receptor studies were performed on human and rat adipocytes and rat hepatocytes. Sulphated insulin displayed a lower affinity for binding to both human and rat adipocytes compared with neutral insulin, approximately four times the concentration being required to achieve half-maximal displacement of monoiodoinsulin (p〈0.05 and 0.01, respectively). A 20-fold higher concentration of sulphated insulin was required for half-maximal displacement from rat hepatocytes (p〈0.025). However, sulphated insulin bound to liver membranes with an affinity more closely resembling that for adipocytes rather than hepatocytes. Differences in the intracellular processing of the negatively charged insulin could account for the observed lower affinity of binding to hepatocytes.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00273803
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  • 10
    Electronic Resource
    Electronic Resource
    Factors in impedance pneumography (1974)
    Springer
    Medical & biological engineering & computing 12 (1974), S. 599-605 
    Details
    ISSN: 1741-0444
    Keywords: Impedance pneumography ; Respiration ; Mathematical models
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Description / Table of Contents: Sommaire Les efforts déployés pour calibrer les impédances transthoraciques mesurées par rapport aux volumes d'air pulmonaire n'ont été couronnés due d'un succès relatif. Nous avons mis au point un modèle analogique non homogène du thorax composé de deux cylindres coaxiaux ayant des résistivités et des dimensions différentes. Les mesures obtenues ont été comparées aux calculs entre lesquels il existait une corrélation étroite. Utilisant ensuite un modèle mathématique et des données caractéristiques d'un adulte de sexe masculin, nous avons calculé les contributions relatives de tous les facteurs en jeu dans la pneumographie par impédance. Nous avons observé que les changements dans le rayon des électrodes, dans la résistivité de la paroi thoracique et dans les diverses dimensions de la cage thoracique contribuent beaucoup plus aux variations d'impédance que les changements de résistivité des poumons; nous avons conclu que la pneumographie par impédance n'a une utilisation clinique que dans la mesure où elle peut permettre de surveiller le rythme respiratoire et l'apnée.
    Abstract: Zusammenfassung Die Bemühungen, gemessene transthorakale Impedanzen auf Grund des Luftvolumens in der Lunge zu eichen, waren nur am Rande erfolgreich. Wir haben ein neues, nicht homogenes Analogmodell des Thorax gefunden, das aus zwei koaxialen Zylindern mit unterschiedlichen spezifischen Widerständen und Abmessungen besteht. Die Messungen wurden mit Berechnungen verglichen und es ergab sich ein enger Zusammenhang. Unter Ver wendung des mathematischen Modells und typischer Werte für männliche Erwachsene berechneten wir die relativen Beiträge aller Faktoren in der Impedanz-Pneumographie. Wir stellten fest daß Änderungen des Elektrodenradius und des spezifischen Widerstands der Brustwand sowie unterschiedliche thorakale Abmessungen mehr zu Impedanzschwankungen beitragen als Änderungen im spezifischen Widerstand der Lunge und schlossen daraus, daß die Impedanz-Pneumographie lediglich klinisch als Monitor für Atmungsgeschwindigkeit und Apnoe eingesetzt werden kann.
    Notes: Abstract Efforts to calibrate measured transthoracic impedances against pulmonary air volumes have been marginally successful. We devised a new nonhomogeneous analogue of the thorax consisting of two coaxial cylinders with different resistivities and dimensions. Measurements were compared with calculations and found to correlate closely. Then, using the mathematical model and data typical of adult male patients, we calculated the relative contributions of all the factors involved in impedance pneumography. We found that changes in electrode radius, chest-wall resistivity and various thoracic dimensions contribute much more to impedance variations than changes in lung resistivity, and conclude that impedance pneumography only has clinical use as a monitor for respiration rates and apnea.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02477221
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