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  • 1
    ISSN: 1432-0428
    Keywords: Isolated islets ; insulin release ; glucagon ; glucose ; cyclic adenosine monophosphate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Glucose stimulation increased the cAMP content of collagenase-isolated rat pancreatic islets fourfold above baseline values. The elevation was transient, lasting about 5 min, and was dose-dependent. Insulin release continued at a constant rate throughout the incubation. — Glucagon, in the absence of glucose, increased cAMP for about 1 min, but only slightly, and had no effect on insulin release. In the presence of glucose, however, glucagon enhanced islet cAMP content 15-fold and increased the release of insulin. Glucagon was most effective at high glucose concentrations (16.6 and 25 mM). — This indicates that glucagon is critically dependent on the presence of glucose in order to increase the islet cAMP content and to stimulate insulin release. The inability of glucagon to generate sufficient cAMP in the absence of glucose might be one of the reasons why the hormone is a potentiator rather than an initiator of insulin release.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0428
    Keywords: Islet hyperplasia ; islet DNA ; islet protein ; insulin release ; tolbutamide treatment ; theophylline
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Following prolonged administration of tolbutamide the DNA- and protein content per islet was enhanced but the IRI content per islet was diminished. Glucose-induced (2.0,8.0 or 16.6 mM) and leucine-induced (12.5 or 25.0 mM) IRI release from isolated islets, as well as 14CO2-production from U-14C glucose, were decreased. Theophylline (5.0 mM) restored the glucose sensitivity of the islets towards normal. The results indicate that tolbutamide-induced islet cell hyperplasia does not entail islet hyperfunction, as previously thought. Decreased IRI release may partially be explained by a tolbutamide-induced alteration of the adenylate cyclase/phosphodiesterase system of the B-cell.
    Type of Medium: Electronic Resource
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  • 3
    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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  • 4
    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.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 10 (1974), S. 85-87 
    ISSN: 1432-0428
    Keywords: Cytochalasin B ; microfilamentous system ; isolated pancreatic islets ; insulin release
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Cytochalasin B (200 μg/ml) completely inhibited the glucose-induced insulin release from isolated rat islets. Basal release was unaffected. The cytochalasin-induced inhibition was rapidly reversible. Pretreatment with cytochalasin B seemed to increase the sensitivity of islets to a subsequent glucose stimulation.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-0428
    Keywords: GIP ; gastrin ; insulin ; incretin ; coeliac disease ; duodeno-pancreatectomy ; chronic pancreatitis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-0428
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1432-0428
    Keywords: Insulinoma ; IRI content of insulinoma ; ultrastructural categorization of insulinomas ; proinsulin content of insulinomas ; functional defect in insulinomas reduced storage capacity of insulinoma cells ; non-granular insulin release ; proinsulin content of human pancreas ; diazoxide response of insulinomas
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Thirty human insulinomas have been investigated histologically and their immunoreactive insulin (IRI) content estimated. In most cases immunohistological and ultrastructural studies were also performed and the percentage of proinsulin-like components (PLC) in the tumour determined. Except for 1 case the IRI concentration in the tumours was lower (0.01–89.0 U/g) than in the islet tissue. Histologically, immunohistologically and ultrastructurally a variable number of tumour cells contained few and often no beta-granules, indicating a decreased storage capacity for insulin. This defective storage capacity seems to be the major functional abnormality of insulinoma cells. Ultrastructurally four types of insulinoma can be distinguished. The ultra-structural diagnosis of an insulinoma can only be made in type I (typical beta-granules, 13 cases) and type II (typical and atypical granules, 7 cases) but not in type III (atypical granules only, 4 cases) and type IV (virtually agranular, 4 cases). The type IV tumours had the lowest IRI concentration and did not respond to diazoxide treatment. The IRI concentration of the uninvolved pancreas of 19 patients was 2.0±0.2 U/g and in the range of non-diabetic adults. — The percentage PLC in 19 insulinomas was higher (5.3–22%) than in the pancreas of human adults with and without insulinoma (1.7–4.8%). The percentage of PLC in the serum of patients with insulinoma was always higher than in their tumours (33–61%). It is suggested that the higher PLC levels found in the tumour and serum of insulinoma patients are the consequence of the reduced storage capacity of the tumour cells resulting in a rapid passage through the granular route or even a non-granular release of newly synthesized insulin.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 8 (1972), S. 250-259 
    ISSN: 1432-0428
    Keywords: Insulinoma ; immunohistologic investigation of B-cell tumours ; peroxidase labelled antibodies ; insulin and C-peptide in B-cells ; insulin concentration of insulinomas ; difference between insulin in normal and tumour B-cells
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé 14 insulinomes ont été soumis à un examen immunohistologique à l'aide de la méthode de l'anticorps marqué à la peroxydase. 8 tumeurs ont été étudiées immédiatement après leur extirpation. 7 d'entre elles réagissaient avec les sérums anti-insuline et anti-porcine-C-peptide, mais non avec le sérum anti-glucagon. Un seul carcinome à cellules B avec un contenu en insuline inhabituellement bas, a été négatif. Un an après l'inclusion dans la paraffine, la réaction immunohistologique avec le sérum anti-insuline avait nettement diminué dans les tumeurs, mais non dans les îlots du pancréas adjacent. Chez 6 patients, on disposait de fragments de la tumeur et du pancréas normal inclus dans la paraffine depuis 1 à 4 ans. Dans ce groupe, 4 tumeurs avec un contenu élevé en insuline, n'avaient qu'une faible réaction immunohistologique avec un sérum antiinsuline, et deux tumeurs (l'une avec un contenu élevé en insuline, l'autre avec un contenu faible) ont eu une réaction immunohistologique négative, tandis que les îlots du pancréas adjacent réagissaient fortement dans les six cas. Donc, la réaction immunohistologique de l'insuline dans les tumeurs à cellules B, mais non dans les îlots normaux, dépend du temps écoulé entre l'inclusion dans la paraffine et le moment où elles sont examinées. Seules les tumeurs fixées dans du liquide de Bouin, mais non dans la solution de Karnovsky, ont eu une réaction immunohistologique positive, tandis que les îlots du pancréas adjacent réagissaient positivement après fixation dans la solution de Karnovsky. Ces résultats suggèrent qu'il existe des différences entre l'insuline du pancréas normal et l'insuline des tumeurs. Une comparaison entre la coloration à l'aldéhyde-thionine et l'immunohistologie indique la supériorité de l'immunohistologie dans l'identification des cellules tumorales produisant de l'insuline.
    Abstract: Zusammenfassung 14 insulinproduzierende Tumoren wurden mittels Peroxydase-markierter Antikörper immunhistologisch untersucht. 8 Tumoren gelangten unmittelbar postoperativ zur Untersuchung. Hiervon ließen sich 7 mit einem Antiserum gegen Insulin und Schweine-C-Peptid, nicht aber mit einem Antiserum gegen Glucagon anfärben. Dagegen reagierte ein B-Zellcarcinom mit einer sehr niedrigen Insulinkonzentration mit keinem dieser Seren. Bereits ein Jahr nach der Einbettung in Paraffin ließ die Anfärbbarkeit dieser Tumoren mit einem Antiinsulinserum deutlich nach, während die Inseln des umgebenden normalen Pankreas mit dem gleichen Serum unverändert stark reagierten. — Von 6 weiteren Inseladenomen standen außerdem 1– 4 Jahre altes paraffineingebettetes Tumor- und Pankreasgewebe zur Verfügung. 4 dieser Tumoren hatten eine erhöhte Insulinkonzentration, reagierten immunhistologisch jedoch mit einem Antiinsulinserum nur schwach. Die beiden restlichen Tumoren — einer mit einer hohen, der andere mit einer niedrigen Insulinkonzentration — verhielten sich immunhistologisch negativ. Im Gegensatz zu den Tumoren ließen sich die Inseln des umgebenden Pankreas sämtlicher 6 Fälle mit einem Insulinantiserum gut anfärben. Somit scheint der erfolgreiche immunhistologische Nachweis von Insulin in insulinproduzierenden Tumoren von der Dauer der Einbettung des Tumormaterials in Paraffin abzuhängen. Das Insulin in den Pankreasinseln unterliegt dagegen diesem „Alterungseffekt“ nicht. — TumorInsulin läßt sich nur in Bouin-fixiertem, nicht aber in Karnovsky-fixiertem Gewebe immunhistologisch nachweisen, während das Insulin des normalen Pankreas auch nach Karnovsky-Fixation immunhistologisch nachweisbar ist. Die Befunde sprechen für Unterschiede zwischen normalem pankreatischen und Tumor-Insulin. — Die Färbung der B-Zellen von Tumoren mit Aldehyd-Thionin gelingt seltener als der immunhistologische Nachweis von Insulin in diesen Zellen. Die immunhistologische Untersuchung ist daher zur Identifizierung von B-Zelltumoren den üblichen spezifischen Färbungen überlegen.
    Notes: Summary 14 insulinomas were examined immunohistologically using the peroxidase labelled antibody method. 8 tumours were investigated immediately after extirpation. 7 of these reacted with insulin and porcine-C-peptide antisera but not with glucagon antiserum. Only a B-cell carcinoma with an unusually low insulin concentration was negative. One year after embedding in paraffin the immunohistologic reaction with insulin antiserum had markedly decreased in the tumours; however, not in the islet of the adjacent pancreas. From 6 patients 1 to 4 years old paraffin-embedded material of the tumour and the normal pancreas was available. In this group 4 tumours with an elevated insulin concentration reacted immunohistologically only weakly with an insulin antiserum and two tumours (one with high and one with low insulin concentration were immunohistologically negative, while the islets of the adjacent panceas of all six cases showed a strong reaction. Thus the immunohistilogic reaction of insulin in B-cell tumours but not in normal islets depends on the time elapsed between the paraffin embedding and the examination. Only tumours fixed in Bouin's fluid but not in Karnovsky's solution gave a positive immunohistologie reaction, while the islets of the adjacent pancreas reacted positively also after fixation in Karnovsky's solution. These findings suggest differences between the normal and the tumour insulin. A correlation between aldehyde-thionin stain and immunohistology indicates the superiority of immunohistology in identifying insulin producing tumour cells.
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  • 10
    ISSN: 1432-0428
    Keywords: Maturity-onset diabetes ; diet ; tolbutamide ; buformin ; body weight ; glucose tolerance ; fasting IRI ; lactate ; pyruvate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: 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.
    Abstract: 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.
    Notes: 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.
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