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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 13 (1977), S. 269-272 
    ISSN: 1432-0428
    Keywords: Insulin secretion ; oral glucose ; reflex insulin secretion ; portal vein ; dog
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Concentrations of immunoreactive insulin activity and of blood glucose were measured in portal and peripheral venous blood in six conscious dogs after oral administration of 1.0 g/kg glucose. Portal venous samples were obtained either by chronic catheterization or by direct puncture of the portal vein through a London-cannula. Portal venous IRI was already significantly increased 5 min after the onset of the stimulus. Peripheral venous IRI pattern reflected this early increase, but the peripheral venous blood glucose level was unchanged. The results indicate that the early peripheral venous IRI increase reflects a pancreatic insulin secretory reflex.
    Type of Medium: Electronic Resource
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  • 2
    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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  • 3
    ISSN: 1432-0428
    Keywords: Insulin secretion rate ; pancreatic blood flow ; mathematic model ; IRI concentration ; blood glucose ; glucose assimilation ; dog
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The pancreaticoduodenal and portal venous blood flows were recorded electromagnetically in anaesthetized dogs. Blood glucose and IRI were measured in the arterial, portal, and peripheral venous as well as in the intestinal venous blood. By a mathematical model the actual net IRI output of the whole pancreas was estimated. Under basal conditions it is 10.2±2.4 mU/min (n = 30; 26 kg mean body wt). After i.v. glucose injection, IRI output is rapidly enhanced. The biphasic nature of this reaction was unequivocally demonstrated by consideration of the ratio IRI output: blood glucose. Pancreaticoduodenal blood flow increases transiently in relation to the increased blood glucose concentration. The IRI secretion rate is well correlated with the blood glucose concentration and to the amounts of glucose or of blood reaching the whole pancreas. It is also correlated with the portal IRI concentration. The overall peripheral venous or arterial IRI concentrations are correlated with the IRI secretion rate, but not in all individual experiments. The different phases of IRI output (basal rate, stimulated output 1–10 min and 10–60 min) show no influence on each other, nor are they correlated with the peripheral IRI concentration area. Basal IRI output is negatively correlated with the glucose assimilation constants. These constants or the peripheral B G areas, however, are independent of the stimulated IRI output rate. However, both the assimilation constants and the peripheral BG areas are related to the peripheral IRI concentration areas. Hepatic uptake of insulin and dynamics of pancreatic blood flow seem to contribute considerably to the estimated correlation pattern.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 21 (1981), S. 51-53 
    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
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  • 5
    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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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 12 (1976), S. 133-136 
    ISSN: 1432-0428
    Keywords: Pancreatic blood flow ; oral glucose test ; insulin secretion ; reflex
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Dogs with an electromagnetic flowprobe implanted around the superior pancreaticoduodenal artery and with an hydraulic occluder implanted upstream from the flowprobe were examined between the 3rd and the 8th postoperative day. During an oral glucose load, blood flow increased from the beginning of administration to about 25 minutes, but not when blood glucose and plasma IRI exhibit their maxima. The rise of pancreatic blood flow is assumed to be produced by reflexes similar to those stimulating insulin secretion and exocrine pancreatic function during the early phase of an oral glucose load.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 7 (1971), S. 6-9 
    ISSN: 1432-0428
    Keywords: Annual rhythm ; eviscerated rabbit ; isolated heart ; insulin action ; glucose uptake ; glycogen ; seasonal variation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé Sur le lapin éviscéré et néphrectomisé et sur le eoeur de rat isolé et perfusé, on a constaté une périodicité circannuelle de l'effet de l'insuline sur la captation du glucose et sur le contenu en glyeogène. Dans des conditions méthodologiques constantes, la même dose de la même préparation insulinique atm effet diminué d'environ 50% pendant les mois d'été. Ces relations ont été prouvées par des observations continues pendant 14 mois et furent projetées sur une année calendaire pour la mise en valeur. Elles sont considérées comme l'expression d'un rythme endogène de l'organisme entier.
    Abstract: Zusammenfassung An eviszerierten nephrektomierten Kaninchen und isolierten perfundierten Rattenherzen wurde eine circannuale Periodizität des Ausmaßes von Insulineffekten auf die Glueoseaufnahme sowie den Glycogenbestand gefunden. Unter konstanten methodischen Gegebenheiten wirkt dieselbe Dosis des gleichen Insulin-präparates in den Sommermonaten etwa 50% weniger, als in den Wintermonaten. Diese Verhältnisse sind durch kontinuierliche Beobachtungen über 14 Monate belegt und zur Auswcrtung auf ein Kalenderjahr projiziert. Sie werden als Ausdruck einer endogenen Rhythmizität des Organismus betrachtet.
    Notes: Summary A seasonal variation in glucose uptake and glycogen content was found in eviscerated nephrectomized rabbits and in isolated perfused rat hearts. In the same methodological circumstances the same dose of the same insulin preparation showed a reduction in effect of about 50% in the summer months. These relations were established by means of continuous observations for 14 months, which have been projected on one calendar year for interpretation. They are accounted for as an expression of the endogenous rhythm of the whole organism.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 8 (1972), S. 104-110 
    ISSN: 1432-0428
    Keywords: Oral glucose tolerance test ; insulin secretion ; feed-forward ; enterohormones ; N.vagus ; reflex
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé Chez des chiens-bergers éveillés et entraînés, après administration orale de glucose, la concentration d'IRI dans le sang veineux périphérique augmente déjà alors que la glycémie n'a pas encore changé. Après un ou deux pics durant les vingt premières minutes, l'IRI augmente parallèlement au glucose sanguin. Comparativement à l'injection intra-veineuse de glucose, le maximum d'IRI, après administration orale, se produit plus tôt. De plus, le quotient des surfaces d'IRI et de glycémie est élevé. Sans aucun changement du glucose sanguin, la concentration d'IRI augmente avec un ou deux pics après administration orale d'eau potable. Ces pics correspondent aux deux premiers pics après administration orale de glucose. Ces résultats sont discutés dans le sens d'une sécrétion d'insuline précédant la digestion via N.vague et via entérohormones. Il faut accorder plus d'attention à l'évolution d'IRI durant la première phase du test de tolérance au glucose par voie orale.
    Abstract: Zusammenfassung Bei wachen trainierten Schäferhunden steigt die Insulinkonzentration im peripheren Venenblut nach oraler Glucosegabe schon zu einem Zeitpunkt an, da die Glykämie noch nicht verändert ist. Nach Durchlaufen von 1 oder 2 Gipfeln in den ersten 20 min tritt der Anstieg ein, der parallel dem Blutzuckergipfel verläuft. Im Verhältnis zur intravenösen Glucosegabe liegt das erste IRI-Maximum nach oraler Verabfolgung zeitlich früher. Auch ist der Quotient aus IRIÜberschreitungsfläche und Blutzuckerüberschreitungsfläche erhöht. Ohne daß es zu einer Blutzucker Veränderung kommt, steigt auch nach oraler Gabe von Leitungswasser die IRI-Konzentration 1-oder 2gipflig an. Diese Gipfel entsprechen den beiden ersten Erhöhungen nach oraler Glucosegabe. Die beobachteten Phänomene werden im Sinne einer Vorwärtskopplung der Insulinsekretion nach Nahrungsaufnahme via N.vagus und Enterohormone diskutiert. Der Beurteilung des IRI-Verlaufs in der frühen Phase des oralen Glucosetoleranztests sollte größere Beachtung geschenkt werden.
    Notes: Summary In conscious trained dogs (Alsatians) the IRI-concentration in the peripheral venous blood after oral administration of glucose increases when the blood glucose is still unchanged. After one or two peaks during the first 20 min IRI increases parallel to the blood sugar increase. In relation to the intravenous injection of glucose the IRI maximum after oral administration occurs earlier. Furthermore the ratio of the IRI to blood sugar areas is raised. Without any blood sugar change the IRI concentration after oral application of tap water increases with one or two peaks. These peaks correspond to the first peaks after oral administration of glucose. These findings are discussed in the sense of a “feed-forward” of insulin secretion after feeding via N.vagus as well as via enterohormones. More attention should be payed to the IRI course during the early phase of the oral glucose tolerance test.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 8 (1972), S. 111-116 
    ISSN: 1432-0428
    Keywords: Oral glucose tolerance ; insulin secretion ; reflex ; sham-feeding ; enterohormones
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé Des chiens éveillés et entraînés portant des fistules de l'oesophage ou de l'estomac ne présentent aucune élévation du sucre sanguin après alimentation simulée de glucose, néanmoins une augmentation considérablede la concentration insulinique dans le sang veineux périphérique apparaît. Celle-ci consiste en deux pics bref s entre la 5 e et la 10 e min et aussi entre la 15 e et la 25 e min. Ces deux pics apparaissent aussi après alimentation simulée d'eau potable, mais à un moindre degré. Leur ordre chronologique correspond aux pics précoces d'IRI que nous avons observés antérieurement, après administration orale de glucose chez des animaux intacts, avant l'élévation glycémique réelle. Après application de glucose dans l'ouverture aborale de la fistule chez des animaux portant une fistule de l'oesophage, il manque le premier pic d'IRI, le deuxième et le troisième pic (provoqués par résorption) apparaissent invariablement. Une insulino-sécrétion intensifiée, couplée à la prise de nourriture et induite par l'ingestion orale est suggérée et discutée dans le cadre de l'«entero-insular axis» du mécanisme de l'insulino-sécrétion.
    Abstract: Zusammenfassung Wache trainierte Hunde mit doppelläufigen Fisteln des Oesophagus oder des Magens zeigen nach Scheinfütterung mit Glucose keinen Blutzucker -anstieg, aber eine sichere Erhöhung des immunchemisch gemessenen Seruminsulins im peripheren Venenblut. Es wurden zwei kurzzeitige Peaks zwischen der 5. und 10. sowie der 15. und 25. min beobachtet. In geringerem Ausmaß fanden sich diese beiden Peaks auch nach Scheinfütterung mit Leitungswasser. Sie entsprechen in ihrer zeitlichen Anordnung den von uns früher beobachteten frühen Insulingipfeln nach oraler Glucosegabe an intakte Tiere vor dem eigentlichen Blutzuckeranstieg. Bei Glucoseverabfolgung in die aborale Fistelöffnung von Oesophagusfistelträgern fehlt der erste IRI-Gipfel, der zweite und der dritte (resorptionsbedingte) sind unverändert ausgeprägt. Es wird eine von Rezeptoren der Mundhöhle ausgelöste Vorwärtskopplung der Insulinsekretion bei oraler Verabfolgung stimulierender Substanzen angenommen und im Rahmen der „enteroinsulinären Achse“ des Insulininkretionsmechanismus diskutiert.
    Notes: Summary After sham-feeding of glucose, conscious trained dogs bearing double-barrelled fistulas of the oesophagus or of the stomach do not show any blood sugar increase. Nevertheless their IRI-levels in the peripheral venous blood increased considerably. This increase consists of two peaks of short duration between the 5th and the 10th as well as the 15th and the 25th min. Such IRI-peaks oceured also after sham-feeding of tap water, but to a smaller extent. Their temporal order corresponds to the early IRI-peaks after oral glucose administration in intact animals, but before the blood glucose increase which was observed by us previously. After the application of glucose into the oral opening of the oesophageal fistula the first IRI-peak does not occur, the second and the third peaks appeared to the same extent. A feed-forward of insulin secretion induced by oral ingestion is suggested. It may be interpreted within the scope of the “entero-insular axis” of the mechanism of insulin secretion.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 8 (1972), S. 385-390 
    ISSN: 1432-0428
    Keywords: Oral glucose tolerance test ; insulin secretion ; reflex ; glucose doses ; receptor ; mucosal anaesthesia ; cyclamate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé Des expériences préalables ont montré que dans un test oral de tolérance au glucose l'insuline est mobilisée au cours de la première phase indépendamment de l'hyperglycémie qui suit. Si l'on administre différentes doses de glucose (0.5–2.0 g/kg) à des chiens éveillés et entrainés, il apparaît que cette première phase de la sécrétion d'insuline est stimulée par des mécanismes additifs indépendamment de la charge de glucose appliquée. Ces mécanismes, au moins en partie, commencent aux terminaisons nerveuses de la cavité buccale: leur paralysie par anesthésie de la muqueuse empêche la première augmentation réflexe d'IRI chez les animaux intacts de même que l'augmentation d'IRI après alimentation simulée de glucose chez des chiens ayant des fistules de l'oesophage. Le fait de pulvériser du cyclamate de sodium dans la cavité buccale ne provoque aucune augmentation d'IRI. Cela signifie que la saveur “sucrée” n'intervient pas dans le mécanisme du réflexe. Les mécanismes des réflexes conditionnés qui sont la conséquence d'un programme d'entraînement ou d'un régime alimentaire journalier étaient exclus par des expériences de contrôle.
    Abstract: Zusammenfassung Vorangegangene Experimente hatten ergeben, daß bei einem oralen Glucosetoleranztest in einer ersten Phase Insulin unabhängig von der erst darauffolgenden Hyperglykämie freigesetzt wird. Durch Gabe unterschiedlicher Glucosedosen (0.5–2.0 g/kg) an wache, trainierte Schäferhunde wird in dieser Mitteilung gezeigt, daß diese erste Phase der Insulinsekretion von der verabfolgten Glucosedosis unabhängig durch zusätzliche Mechanismen stimuliert wird. Diese Mechanismen beginnen zumindest teilweise in Nervenendigungen der Mundhöhle: ihre Betäubung durch Schleimhautanästhesie verhindert den frühzeitigen reflektorischen IRI-Anstieg bei intakten Tieren sowie den gleichen reflektorischen IRI-Anstieg nach Glucosescheinfütterung an Hunde mit Oesophagusfisteln. Einstäuben von Natrium-Zyklamat in die Mundhöhle ruft keinen IRI-Anstieg hervor. Die Geschmacksrichtung „süß” ist also nicht an den reflektorischen Mechanismen beteiligt. Bedingt-reflektorische Vorgänge als Folge des Trainingsprogramms oder der täglichen Nahrungsaufnahme wurden durch Kontrollversuche ausgeschlossen.
    Notes: Summary Previous experiments have shown that in an oral glucose tolerance test insulin is mobilized in the first phase independent of the following hyperglycemia. By giving different amounts of glucose (0.5–2.0 g/kg) in conscious trained dogs it was shown that this early phase of insulin secretion was stimulated independently of the administered glucose load by additional mechanisms. These mechanisms, at least partly, were triggered in the nerve endings of the cavity of mouth: their paralysis by mucosal anaesthesia abolished the early IRI-increase in intact animals as well as after feeding glucose to dogs bearing oesophagus fistulas. Spraying sodium cyclamate into the mouth did not produce any IRI-increase. The results indicate that the taste modality “sweet” is not involved in this reflex response. Conditioned reflexes as a consequence of the training programme or of the daily feeding regime were excluded by control experiments.
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