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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 11 (1975), S. 113-117 
    ISSN: 1432-0428
    Keywords: Bile salt absorption ; biguanides ; phenformin ; buformin ; metformin ; active transport ; bile salt malabsorption
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0428
    Keywords: GIP ; gastrin ; insulin ; incretin ; chronic pancreatitis ; test meal ; malassimilation of fat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-0428
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé Le métabolisme des foies isolés perfusés des rats normaux et des rats alloxane-diabétiques cétosiques a été étudié et comparé. Des milieux de perfusion avec des concentrations différentes de NEFA ont été employés. — Si la concentration du glucose dans le milieu est élevée de 11.1 à 22.2 mmole/l, la captation et l'utilisation du glucose ainsi que la formation de glycogène augmentent, la sécrétion de phosphate inorganique diminue. — On peut diviser les 3 heures de perfusion des foies normaux en deux phases: la première phase est caractérisée par une glyconéogenèse intensive et simultanément par une oxydation plus forte d'acides gras. Pendant la seconde phase, l'utilisation du glucose domine et l'oxydation des acides gras diminue. — Les perfusions des foies diabétiques comparés avec les foies normaux, donnent les résultats suivants: le glycogène au début est élevé, la production de glycogène est plus forte. Au début de la perfusion, la concentration de lactate dans le milieu est élevée, la concentration de pyruvate est abaissée. Le quotient lactate/pyruvate est élevé, mais il se normalise au cours de la perfusion; les différences sont significatives. La captation nette de lactate et de pyruvate pendant la première phase est encore plus forte dans les expériences avec des foies diabétiques. L'augmentation de la sécrétion nette d'urée et de potassium des foies diabétiques est significative. Il n'y a pas de différences significatives dans la captation de NEFA entre les foies normaux et diabétiques. Les rapports entre l'absorption des NEFA et la formation de corp cétoniques sont inchangés dans les foies diabétiques.
    Abstract: Zusammenfassung Der Stoffwechsel isolierter perfundierter Lebern von normalen und alloxandiabetischen ketotischen Ratten wurde vergleichend untersucht. Dabei wurden Perfusionsmedien mit unterschiedlichem NEFA-Gehalt verwendet. — Glucoseaufnahme, Glucoseutilisation, Glykogenbildung nehmen zu, die Abgabe von anorganischem Phosphat ab, wenn die Glucosekonzentration im Medium von 11.1 auf 22.2 mMol/l erhöht wird. — Während der 3-stündigen Perfusion normaler Lebern lassen sich zwei Phasen unterscheiden: Die erste Phase wird bestimmt durch eine stärkere Gluconeogenese bei gleichzeitiger stärkerer Fettsäureoxydation, in der zweiten Phase überwiegt die Glucoseutilisation bei verminderter Fettsäureoxydation. Perfusionsversuche mit diabetischen Lebern lassen folgende Unterschiede erkennen: Der Ausgangsglykogengehalt ist ebenso signifikant erhöht wie der Glykogenzuwachs während der Perfusion. Die Lactatkonzentrationen im Medium sind zu Versuchsbeginn signifikant erhöht, die Pyruvatkonzentrationen signifikant erniedrigt. Der Lactat/Pyruvat-Quotient im Medium ist zu Versuchsbeginn signifikant erhöht, normalisiert sich aber im Verlauf der Perfusion. Die in der ersten Versuchshälfte nachweisbare Nettoaufnahme von Lactat und Pyruvat ist in Versuchen mit diabetischen Lebern verstärkt. Die Nettoabgabe von Harnstoff und Kalium durch diabetische Lebern ist signifikant verstärkt. Die Kinetik der NEFA-Aufnahme ergibt keinen signifikanten Unterschied zwischen normalen und diabetischen Lebern. Diabetische Lebern weisen keine signifikanten Änderungen der Beziehungen zwischen NEFA-Aufnahme und Ketonkörperbildung auf.
    Notes: Summary The metabolism of isolated perfused livers from alloxan-diabetic ketotic rats was compared with that of livers from normal animals. Perfusion media with different contents of nonesterified fatty acids (NEFA) were used. An increase in the concentration of glucose in the medium from 11.1 to 22.2 mmole/l augmented glucose uptake, glucose utilization and formation of glycogen, while the net production of inorganic phosphate decreased. During the 3 hours of perfusion, two phases could be observed in experiments with livers from normal rats: The first phase was characterized by both a greater gluconeogenesis and a greater oxidation of fatty acids. During the second phase fatty acid oxidation decreased while glucose utilization prevailed. Perfusion experiments with livers from diabetic rats yielded the following results when compared with livers from normal rats: the liver glycogen content at the beginning of the perfusion as well as the increase in the glycogen content during the perfusion was significantly increased; at the beginning of the experiments the medium concentrations of lactate were significantly higher and the concentrations of pyruvate significantly lower; the lactate/pyruvate ratio of the medium at the beginning of the experiments was significantly higher although it became the same as the normal during the perfusion. The net uptake of lactate and pyruvate, which could be observed under all conditions during the first 90 min of the perfusion, was distinctly increased in experiments with diabetic livers. The net production of urea and the release of potassium ions were significantly higher in experiments with diabetic livers. The kinetics of NEFA-uptake by normal and diabetic livers did not show a significant difference. The correlation between NEFA-uptake and ketone body-formation was the same in diabetics as in normal livers.
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  • 4
    ISSN: 1432-0428
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé Continuant les expériences précédentes, l'influence de l'insuline sur le métabolisme des foies isolés des rats normaux et alloxane-diabétiques a été étudiée. De milieux de concentrations différentes d'acides gras nonestérifiés (NEFA) (2.5–3.5 mEq/l et 0.30–0.65 mEq/l) ont été employés. Dans toutes ces expériences 0.9 U/h d'insuline ont été infusées dans la veine porte pendant la durée de l'expérience (180 min). Les résultats suivants ont été obtenus: 1. La captation nette de glucose par des foies normaux est augmentée par l' insuline de façon significative; le bilan net du glucose des foies diabétiques est inchangé. Sous l'influence de l'insuline la synthèse de glycogène intensifiée diminue. 2. L'insuline provoque une diminution significative de la sécrétion d'acides α-aminés et une captation nette d'acides α-aminés. La production d'urée des foies normaux n'est pas influencée par l'insuline, tandis que celle des foies diabétiques diminue un peu, mais pas de façon significative. 3. L'accroissement retardé des concentrations de lactate et de pyruvate des foies diabétiques — comparé aux foies normaux — est un peu accéléré, mais pas de façon significative, par l'insuline. Le quotient lactate/pyruvate (L/P-Q) ainsi que les concentrations de potassium et de phosphate inorganique ne sont pas influencés par l'insuline, ni dans les foies normaux, ni dans les foies diabétiques. Il en est de même avec l'irrigation sanguine du foie. L'insuline provoque une augmentation non significative de la production de bile des foies normaux et diabétiques. 4. Les effets de l'insuline ne dépendent pas des concentrations de NEFA du milieu. Ces résultats démontrent un effet immédiat et direct de l'insuline sur le métabolisme du foie.
    Abstract: Zusammenfassung In Fortsetzung vorausgegangener Experimente [23] wurde der Einfluß von Insulin auf den Stoffwechsel isolierter Lebern von normalen und alloxandiabetischen Ratten untersucht. — Dabei wurden Medien unterschiedlicher Konzentration an unveresterten Fettsäuren (NEFA) (2.5–3.5 mval/l und 0.30–0.65 mval/l) verwendet. In allen Versuchen wurden vom Versuchsbeginn an über die ganze Versuchsdauer von 180 min hinweg 0.9 E Insulin/h intraportal infundiert. Dabei wurden fol. gende Befunde erhoben: 1. Die Nettoglucosebilanz normaler Lebern wurde durch Insulin im Sinne einer signifikanten Steigerung der Glucoseaufnahme beeinflußt, während die Nettoglucosebilanz der Leber von diabetischen Tieren unbeeinflußt blieb. Die verstärkte Glykogensynthese diabetischer Lebern wurde durch Insulin vermindert. 2. Insulin führte zu einer signifikanten Verminderung der Nettoaminosäureabgabe bzw. zu einer Nettoaufnahme von α-Aminosäuren. Die Harnstoffbildung normaler Lebern wurde durch Insulin nicht beeinflußt, diejenige der diabetischen Lebern etwas, aber nicht signifikant gesenkt. 3. Der in Experimenten mit diabetischen Lebern im Vergleich zu normalen Lebern verzögert erfolgende Anstieg der Mediumkonzentrationen von Lactat und Pyruvat wurde durch Insulin etwas, aber noch nicht signifikant gesteigert. Das Verhalten des Lactat/Pyruvat-Quotienten (L/P-Q) im Medium sowie der Konzentrationen von Kalium und anorganischem Phosphat ließ weder in Experimenten mit normalen noch in solchen mit diabetischen Lebern eine signifikante Beeinflussung durch Insulin erkennen. Das gleiche gilt für die Größe der Leberdurchblutung. Die Galleproduktion normaler und diabetischer Lebern war unter Insulin etwas, aber noch nicht signifikant erhöht. 4. Die Untersuchungen ergaben keine Abhängigkeit der Insulinwirkung vom NEFA-Gehalt des Mediums. Die mitgeteilten Befunde sprechen für einen direkten Soforteffekt von Insulin auf den Leberstoffwechsel.
    Notes: Summary Continuing previous experiments the influence of insulin on the metabolism of isolated perfused livers of normal and alloxan-diabetic rats was studied. In these experiments media with different concentrations of nonesterified fatty acids (NEFA) (2.5–3.5 mEq/l and 0.30–0.65 mEq/l were used. In all experiments 0.9 U of insulin/hr were infused intraportally throughout the experiment (180 min). The following results were obtained: 1. Insulin significantly increased the net glucose uptake of normal livers. The net glucose balance of livers from diabetic animals was not affected by insulin. Insulin diminished the increased glycogen synthesis of diabetic livers. 2. Insulin caused a significant decrease in the net amino acid production and a net uptake of α-amino acids. The net production of urea by normal livers was not influenced by insulin, while the urea production of diabetic livers showed a slight but insignificant decrease. 3. The delayed increase in the medium concentrations of lactate and pyruvate in experiments with diabetic livers, as opposed to normal livers, was distinctly, though not significantly accelerated by insulin. The lactate/pyruvate ratio (L/P-Q) of the medium, as well as the concentrations of potassium and inorganic phosphate ions in the medium were not significantly affected by insulin in experiments either with normal or with diabetic livers. The same was observed also in the magnitude of the liver blood flow. During insulin infusion the bile production by normal and diabetic livers rose slightly but not significantly. 4. The experiments did not show the effect of insulin to be dependent on the NEFA-content of the medium. Our data demonstrate a direct and immediate effect of insulin on liver metabolism.
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  • 5
    ISSN: 1432-0428
    Keywords: Isolated islets ; tissue culture ; insulin release ; cyclic AMP ; gastric inhibitory polypeptide ; perifusion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Several insulinotropic hormones have been shown to increase the level of cyclic AMP in isolated islets. This study was performed to investigate whether gastric inhibitory polypeptide (glucose-dependent insulin-releasing polypeptide) has a similar effect, in particular at concentrations close to the physiological level in blood. Collagenase isolated rat islets were maintained for 24 h in tissue culture (medium 199) and then incubated for 30 min for measurement of insulin release and cyclic AMP content. Glucose-induced (16.7 mmol/ 1) insulin release was enhanced by gastric inhibitory polypeptide 1–100 ng/ml (0.196–19.6 nmol/l) in a dose-related fashion. The cyclic AMP content was enhanced only by 100 ng/ ml. However, when 0.1 mmol/l of the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine was present, even 1 ng/ ml of gastric inhibitory polypeptide increased both cyclic AMP content and insulin release. Such a concentration of the hormone can be measured in human blood after a meal. In contrast, in freshly isolated islets no effect of the hormone on glucose-induced insulin release or cyclic AMP content could be detected for concentrations ranging from 1 to 100 ng/ml. These findings demonstrate that the hormone sensitivity of isolated islets is markedly enhanced by short-term maintenance in tissue culture. The results suggest that an increase in cyclic AMP is seen in response to gastric inhibitory polypeptide and may be causally related to the insulinotropic effect of the hormone.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-0428
    Keywords: Glucagon-like peptide-1 ; glucagon-like peptide-2 ; insulin release ; glucose dependency ; isolated islets
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Glucagon-like peptide-1 and glucagon-like peptide-2 are encoded by the m-RNA of pancreatic preproglucagon. They show high conservation in different species and substantial sequence homology to glucagon. Because no definite biological activity of these peptides has been reported, we investigated the effect of synthetic C-terminally amidated glucagon-like peptide-1 [1–36] and synthetic human glucagon-like peptide-2 [1–34] with a free C-terminus on insulin release from isolated precultured rat pancreatic islets in the presence of glucose. Glucagon-like peptide-1 stimulates insulin release at 10 and 16.7 mmol/l glucose in a dose-dependent manner. Significant stimulation starts at 2.5 nmol/l in the presence of 10 mmol/l glucose and near maximal release is observed at 250 nmol/l, with approximately 100% increase over basal at both glucose concentrations. The peptide reaches 63% of the maximal stimulatory effect of glucagon. No stimulation occurs in the presence of 2.8 mmol/l glucose. Glucagon-like peptide-2 has no effect on insulin secretion at any glucose concentration tested. It is concluded that glucagon-like peptide-1, in contrast to glucagon-like peptide-2, exhibits a glucose-dependent insulinotropic action on isolated rat pancreatic islets similar to that of glucagon and gastric inhibitory polypeptide.
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  • 7
    ISSN: 1432-0428
    Keywords: GIP release ; chronic pancreatitis ; steatorrhea ; maldigestion ; pancreatin ; incretin effect
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The influence of impaired digestion on nutrient induced release of gastric inhibitory polypeptide (GIP) and insulin have been investigated in patients with chronic pancreatitis. All patients had massive steatorrhea (〉25 g/24 h), and glucose intolerance. A standard liquid test meal comprising fat and glucose were ingested with or without pancreatic enzyme substitution (9.0 g pancreatin). In the presence of pancreatin the response of serum levels of GIP to the test meal was significantly enhanced (81.2 vs 194.5 μg/l×180 min). Concurrently, the insulin response was augmented (3.4 vs 6.4 U/l×180 min), resulting in improved glucose tolerance. Addition of pancreatin also significantly augmented the GIP response to oral fat (100g), but not to oral glucose (100g). In patients with pancreatogenic steatorrhea the insulin response to an IV glucose infusion (0.7g/ kg/h for 90 min) was augmented by oral fat only after addition of 9.0 g pancreatin to the fat load (3.5 vs 7.3 U/l×180 min). After restoration of the GIP response to fat by pancreatin, the inhibitory effect of IV glucose on fat-induced GIP increase was restored. These data indicate that the GIP response to a mixed meal or triglycerides is dependent on the absorption of nutrients. In patients with chronic pancreatitis improvement of pancreatogenic insufficiency reverses the impaired GIP response, restores the incretin effect of fat, and improves glucose tolerance.
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 2 (1966), S. 269-276 
    ISSN: 1432-0428
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé Le diazoxide, dérivé des thiazides et sans effet diurétique, dont l'action hyperglycémiante est connue depuis longtemps, empêche la sécrétion d'insuline stimulée par le glucose, du pancréas isolé du rat, du lapin et du cochon-nain in vitro. La concentration la plus faible nécessaire pour l'inhibition de la sécrétion d'insuline correspond aux doses thérapeutiques. Le tolbutamide abolit l'inhibition par le diazoxide. 5 préparations de thiazides employées comme diurétiques auxquelles on a attribué une action diabétogéne n'avaient pas d'influence sur la sécrétion d'insuline du pancréas isolé du lapin.-Nos recherches démontrent que l'inhibition de la sécrétion d'insuline doit être une des causes essentielles de l'hyperglycémie provoquée par le diazoxide. En même temps, elles sont en contradiction avec l'opinion que cette inhibition de la sécrétion soit seulement la conséquence d'une libération d'adrénaline stimulée par le diazoxide.
    Abstract: Zusammenfassung Das nichtdiuretisch wirkende Thiazidderivat Diazoxide, dessen hyperglykämische Wirkung seit langem bekannt ist, hemmt in vitro die mit Glucose stimulierte Insulinabgabe des isolierten Pankreas der Ratte, des Kaninchens und des Zwergschweins.-Die für die Hemmung der Insulinabgabe notwendige Konzentration (ab 5μg/ml) des Diazoxide liegt in einem Bereich, der auch bei der Gabe therapeutisch wirksamer Dosen erreicht wird. Tolbutamid hebt die Hemmwirkung des Diazoxide auf. Fünf Thiazidpräparate, die als Diuretika Verwendung finden und denen ebenfalls eine sogenannte diabetogene Nebenwirkung zugeschrieben wird, hatten keinen Einfluβ auf die Insulinabgabe des isolierten Kaninchenpankreas.-Unsere Untersuchungen zeigen, daß die Hemmung der Insulinsekretion eine wesentliche Teilursache der Diazoxide-Hyperglykämie sein muß. Sie sprechen gleichzeitig gegen die Ansicht, die Sekretionshemmung sei nur Folge einer durch Diazoxide gesteigerten Adrenalinfreisetzung.
    Notes: Summary The nondiuretic, hyperglycemia-producing thiazide derivative Diazoxide, inhibits the glucose-stimulated insulin release from the isolated pancreas of the rat, the rabbit, and the miniature pigin vitro. Tolbutamide prevents the inhibitory Diazoxide effect. The lowest concentrations of Diazoxide (5μg/ml) necessary for the inhibition of insulin release are in the same range as therapeutic doses. Five thiazide preparations, commonly used as diuretics and known for their possible so-called diabetogenic side effect, did not have any influence on the insulin release from the isolated rabbit pancreas. The results of our experiments indicate an inhibition of insulin secretion as an important etiological factor in the mechanism of Diazoxide-hyperglyeemia. They do not corroborate those observations that show the inhibition of insulin secretion to be induced by a Diazoxide-mediated epinephrine release.
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 18 (1980), S. 82-82 
    ISSN: 1432-0428
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1432-0428
    Keywords: GIP release ; insulin release ; obesity ; glucose intolerance ; starvation ; food restriction ; weight reduction ; oral glucose load ; test meal ; triglyceride ingestion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The response of serum immunoreactive gastric inhibitory polypeptide (IR-GIP) and immunoreactive insulin (IRI) to a liquid mixed test meal, glucose or fat has been examined in obese subjects before and after starvation or reduced caloric intake (800 calories). Basal serum levels of IR-GIP increased significantly during starvation of obese persons and remained elevated over the whole starvation period while basal serum IRI levels decreased. The exaggerated IR-GIP response of obese subjects with normal or pathological glucose tolerance to a test meal and of obese subjects with glucose intolerance to 100 g glucose ingestion decreased significantly after starvation or food restriction. Simultaneously, the serum IRI response decreased. The exaggerated IR-GIP response of obese subjects to oral triglycerides which did not affect serum IRI or glucose levels was also significantly decreased after food restriction. The IR-GIP response of obese subjects to a test meal was already reduced after 5 days of food restriction together with an improved glucose tolerance. At this stage the IRI response was unchanged. After weight reduction in obese subjects there was a significant decrease of the IRI response to oral but not to intravenous glucose, while the glucose response decreased irrespectively of the mode of glucose administration. The IR-GIP response decreased only after oral glucose. The data are compatible with the hypothesis that the exaggerated IR-GIP response of obese subjects to oral glucose or fat load is secondary to the increased food intake and that changes in IRI response to oral glucose are related to changes in IR-GIP response.
    Type of Medium: Electronic Resource
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