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  • 1
    Digitale Medien
    Digitale Medien
    Springer
    Diabetologia 11 (1975), S. 113-117 
    ISSN: 1432-0428
    Schlagwort(e): Bile salt absorption ; biguanides ; phenformin ; buformin ; metformin ; active transport ; bile salt malabsorption
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary The effect of blood sugar lowering biguanides (phenethyl-, butyl- and dimethylbiguanide) upon jejunal and ileal transport of bile salts (tauro- and glycocholate) was tested in rat small intestine by an in vitro technique. Biguanides inhibited active transport of bile salts in the ileum, but did not affect diffusional absorption of bile salts in the jejunum. The inhibitory effect was time-dependent and not reversible under in vitro incubation conditions, suggesting that biguanides must enter intestinal mucosal cells in order to exert their inhibitory action on active transport of glucose analogues, amino acids, calcium and bile salts. Since biguanides achieve high tissue concentrations in the small intestine even after parenteral administration, inhibition of ileal bile salt reabsorption by biguanides could possibly explain the lipid- and cholesterol-lowering effect of these oral antidiabetic drugs.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 2
    ISSN: 1432-0428
    Schlagwort(e): GIP ; insulin ; incretin ; enteroinsular axis ; rat gut extract ; intestinal hormones
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary The action of watery rat gut extracts on glucose-induced insulin release in anaesthetized rats was examined before and after removal of GIP by immunoadsorption. Infusions of GIP-containing rat gut extracts nearly doubled the insulin release induced by intravenous glucose (1g · kg−1 · h−1). Peak insulin secretion was 98±11 mU/l (mean±SEM) after intravenous glucose and increased to 178±16 mU/l following infusion of glucose plus gut extract (p〈0.005). After injection of GIP antiserum in sufficient amounts to neutralize the GIP activity in the gut extract preparation, the additional insulin release due to the gut extract was reduced by only 30%. After complete removal of GIP from gut extracts by immunoabsorption, more than 50% of the incretin effect remained. These data suggest that the insulinotropic activity of rat gut extracts can only be partially related to GIP. The existence of additional insulinotropic gut factors which may also be released following oral glucose is postulated.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 3
    ISSN: 1432-0428
    Schlagwort(e): Maturity-onset diabetes ; diet ; tolbutamide ; buformin ; body weight ; glucose tolerance ; fasting IRI ; lactate ; pyruvate
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Beschreibung / Inhaltsverzeichnis: Résumé Après une période de contrôle de 5 semaines, on a étudié, pendant 8 semaines, chez 103 diabétiques d'âge mûr l'effet thérapeutique du tolbutamide et de la buformine, ainsi que de leur association, sur la tolérance au glucose, l'IRI à jeun, le taux de lactate et de pyruvate. Dans les groupes traités avec la buformine, on a observé une chute de poids significative. Lors du traitement par le tolbutamide, il ne se produisait pas de réduction du poids. Dans tous les groupes étudiés, les valeurs du glucose diminuaient. Lors de la monothérapie avec la buformine les valeurs de l'IRI à jeun avaient tendance à baisser à la fin de la période de traitement. Lors de l'introduction d'une thérapeutique par le tolbutamide, les valeurs de l'IRI à jeun avaient temporairement tendance à monter. — Lors du traitement par la buformine, on n'a pas observé d'augmentation significative des concentrations de lactate et des quotients lactate/pyruvate. De même, lors du traitement par le tolbutamide, les taux de lactate n'étaient pas modifiés. Après introduction d'un traitement par le tolbutamide, les concentrations de pyruvate étaient significativement plus basses à la fin de la période de traitement.
    Kurzfassung: Zusammenfassung An 103 Altersdiabetikern wurde nach einer 5 wöchigen Kontrollperiode 8 Wochen lang der therapeutische Effekt von Tolbutamid und Buformin, sowie deren Kombination hinsichtlich Glucosetoleranz, Nüchtern-IRI, Lactat- und Pyruvatspiegel untersucht. In den mit Buformin behandelten Gruppen trat ein signifikanter Gewichtsabfall ein. Unter Tolbutamidbehandlung trat keine Gewichtsreduktion, ein. In allen untersuchten Kollektiven sanken die Glucosewerte ab. Bei einer Monotherapie mit Buformin zeigten die Nüchtern-IRI-Werte am Ende der Behandlungsperiode eine abfallende Tendenz. Bei Einleitung einer Tolbutamid-behandlung hatten die Nüchtern-IRI-Werte vorüber-gehend eine ansteigende Tendenz. — Ein signifikanter Anstieg der Lactatkonzentrationen und der Lactat/Pyruvat-Quotienten wurde unter Buforminbehandlung nicht beobachtet. Auch unter Tolbutamidbehandlung änderten sich die Lactatspiegel nicht. Nach Einleitung einer Tolbutamidbehandlung lagen die Pyruvatkonzentrationen am Ende der Behandlungsperiode signifikant niedriger.
    Notizen: Summary The effects of the administration of tolbutamide, buformin or their combination for 8 weeks on glucose tolerance, fasting IRI and lactate and pyruvate levels in 103 maturity-onset diabetics have been compared with corresponding values during a preceding control period of 5 weeks. The group on buformin showed a significant weight loss. There was no weight loss during tolbutamide treatment. Glucose levels decreased in all groups investigated. Fasting IRI levels showed a tendency to decrease at the end of the buformin monotherapy period. There was a transient tendency for fasting IRI levels to increase at the beginning of tolbutamide therapy. — A significant increase of lactate concentrations and of the lactate/pyruvate quotient was not observed during buformin treatment, nor did tolbutamide induce a change in lactate levels. Pyruvate levels were significantly lowered towards the end of the tolbutamide period.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 4
    ISSN: 1432-0428
    Schlagwort(e): GIP ; gastrin ; insulin ; incretin ; chronic pancreatitis ; test meal ; malassimilation of fat
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Twenty-nine patients with chronic pancreatitis had a significantly greater IR-GIP response to a test meal than 15 controls. This increased response was not related to the degree of steatorrhoea or glucose intolerance. It was most marked in a group of patients with moderately impaired IRI release and medium steatorrhoea. From this is concluded that the IR-GIP response to a test meal is determined by at least two factors: 1. feedback control via insulin secretion, 2. assimilation of fat. In chronic pancreatitis endocrine insufficiency may induce an exaggerated GIP response and severe exocrine insufficiency may prevent fat induced GIP release. Gastrin is not involved in the different GIP response in patients with chronic pancreatitis.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 5
    ISSN: 1432-0428
    Schlagwort(e): Keywords GLP-1 [7 ; 36 amide] ; incretin ; insulin ; glucagon ; pharmacokinetics.
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Intravenous glucagon-like peptide (GLP)-1 [7–36 amide] can normalize plasma glucose in non-insulin-dependent diabetic (NIDDM) patients. Since this is no form for routine therapeutic administration, effects of subcutaneous GLP-1 at a high dose (1.5 nmol/kg body weight) were examined. Three groups of 8, 9 and 7 patients (61 ± 7, 61 ± 9, 50 ± 11 years; BMI 29.5 ± 2.5, 26.1 ± 2.3, 28.0 ± 4.2 kg/m2; HbA1 c 11.3 ± 1.5, 9.9 ± 1.0, 10.6 ± 0.7 %) were examined: after a single subcutaneous injection of 1.5 nmol/kg GLP [7–36 amide]; after repeated subcutaneous injections (0 and 120 min) in fasting patients; after a single, subcutaneous injection 30 min before a liquid test meal (amino acids 8 %, and sucrose 50 g in 400 ml), all compared with a placebo. Glucose (glucose oxidase), insulin, C-peptide, GLP-1 and glucagon (specific immunoassays) were measured. Gastric emptying was assessed with the indicator-dilution method and phenol red. Repeated measures ANOVA was used for statistical analysis. GLP-1 injection led to a short-lived increment in GLP-1 concentrations (peak at 30–60 min, then return to basal levels after 90–120 min). Each GLP-1 injection stimulated insulin (insulin, C-peptide, p 〈 0.0001, respectively) and inhibited glucagon secretion (p 〈 0.0001). In fasting patients the repeated administration of GLP-1 normalized plasma glucose (5.8 ± 0.4 mmol/l after 240 min vs 8.2 ± 0.7 mmol/l after a single dose, p = 0.0065). With the meal, subcutaneous GLP-1 led to a complete cessation of gastric emptying for 30–45 min (p 〈 0.0001 statistically different from placebo) followed by emptying at a normal rate. As a consequence, integrated incremental glucose responses were reduced by 40 % (p = 0.051). In conclusion, subcutaneous GLP-1 [7–36 amide] has similar effects in NIDDM patients as an intravenous infusion. Preparations with retarded release of GLP-1 would appear more suitable for therapeutic purposes because elevation of GLP-1 concentrations for 4 rather than 2 h (repeated doses) normalized fasting plasma glucose better. In the short term, there appears to be no tachyphylaxis, since insulin stimulation and glucagon suppression were similar upon repeated administrations of GLP-1 [7–36 amide]. It may be easier to influence fasting hyperglycaemia by GLP-1 than to reduce meal-related increments in glycaemia. [Diabetologia (1996) 39: 1546–1553]
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 6
    ISSN: 1432-0428
    Schlagwort(e): GIP ; gastrin ; insulin ; incretin ; coeliac disease ; duodeno-pancreatectomy ; chronic pancreatitis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary The response of serum immunoreactive gastric inhibitory polypeptide (IR-GIP), gastrin (IRG) and insulin (IRI) to a mixed standard meal was measured in 15 controls, 6 patients with coeliac disease, 26 patients with chronic pancreatitis and 6 patients with chronic pancreatitis and partial duodenopancreatectomy (Whipple's procedure). Serum levels of IR-GIP, IRG and IRI were significantly reduced in patients with coeliac disease. The serum glucose increase was significantly smaller only during the first hour after the meal. Since small intestinal GIP- and G-cells are situated mainly in the glands of duodenal and jejunal mucosa their absolute number is not significantly reduced in coeliac disease. It is suggested that the release of IR-GIP and duodenal IRG is influenced by the rate of absorption of nutrients. In patients with chronic pancreatitis the IR-GIP release is significantly greater than in controls, the IRG release normal and the IRI response delayed. After Whipple's procedure the IR-GIP response is increased significantly while the IRG secretion is abolished. This demonstrates that the duodenum is not necessary for GIP release and that pancreatic and jejunal gastrin are without clinical significance.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 7
    ISSN: 1432-0428
    Schlagwort(e): Maturity-onset diabetes ; controlled comparative study ; diet ; tolbutamide ; buformin ; free fatty acids ; ketone bodies ; triglycérides ; cholesterol
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Beschreibung / Inhaltsverzeichnis: Résumé 100 diabétiques d'âge mûr ont été gardés pendant 13 semaines sous contrôle clinique rigoureux, et on a étudié une série de paramètres sous l'influence d'un traitement avec le tolbutamide et la buformine. Mis à part l'effet du contrôle uniquement diététique, on peut admettre les propriétés pharmacodynamiques suivantes: — 1. La buformine, à la dose de 3 × 100 mg, provoque une augmentation significative des FFA et des corps cétoniques, une chute du cholestérol, sans action précise sur les triglycérides. — 2. Le tolbutamide, à la dose de 1 à 2 g, provoque une chute légère, non-significative des FFA et des corps cétoniques sans action précise sur le cholestérol et les triglycérides. — Ces résultats sont pour la plupart en accord avec les données de la littérature. Il faut noter l'influence exercée par les biguanides sur le métabolisme des acides gras et des corps cétoniques, fait non encore décrit jusqu'à maintenant; ceci peut s'expliquer avant tout par l'abaissement du taux d'insuline.
    Kurzfassung: Zusammenfassung 100 Altersdiabetiker wurden über 13 Wochen in strenger klinischer Kontrolle gehalten und dabei eine Reihe von Parametern unter Einfluß einer Behandlung mit Tolbutamid und Buformin untersucht. Über den Effekt einer rein diätetischen Kontrolle hinaus ließen sich folgende pharmakodynamische Eigenschaften wahrscheinlich machen: — 1. Buformin bewirkt in einer Dosierung von 3 × 100 mg einen signifikanten Anstieg der FFS und Ketonkörper, einen Abfall des Cholesterins ohne deutliche Wirkung auf die Triglycéride. — 2. Tolbutamid bewirkt in einer Dosierung von 1 bis 2 g einen leichten, nicht signifikanten Abfall der FFS und der Ketonkörper ohne deutliche Wirkung auf das Cholesterin und die Triglycéride. — Diese Ergebnisse stehen zum großen Teil in Einklang mit den Daten der Literatur. Bemerkenswert erscheint der bisher noch nicht beschriebene Einfluß der Biguanide auf den Fettsäure- und Ketonkörperstoffwechsel, der wohl am ehesten durch die Senkung des Insulmspiegels erklärt werden kann.
    Notizen: Summary 100 maturity-onset diabetics were kept under strict clinical supervision for 13 weeks, and the influence of a treatment with buformin or tolbutamide on several parameters was investigated. Beyond the effect of dietetic control as such, the following pharmaco-dynamic properties could be shown: — 1. buformin in a dosage of 3 × 100 mg/day leads to a significant increase of FFA and ketone bodies and to a decrease of cholesterol without an unequivocal effect on triglycerides; — 2. tolbutamide in a dosage of 1–2 g/day induces a slight, not significant decrease of FFA and ketone bodies without an unequivocal effect on cholesterol and triglycerides. — These results agree to a large extent with data in the literature. A remarkable and hitherto undescribed influence of biguanides on fat and ketone body metabolism was observed, which is best explained by the lowering of insulin levels.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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