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  • Somatostatin  (4)
  • isolated pancreatic islets  (3)
  • Glibenclamide  (2)
  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 54 (1976), S. 173-175 
    ISSN: 1432-1440
    Keywords: Somatostatin ; ACTH-Sekretion ; Nebennierenrindeninsuffizienz ; Somatostatin ; ACTH secretion ; Adrenal insufficiency
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Somatostatin (250 µg as a bolus i.v. and 250 µg as a 1-hr infusion) was administered to 5 patients with adrenal insufficiency of different origin. In each patient a sustained, progressive fall in plasma ACTH was observed during the infusion period. The mean maximal reduction in plasma ACTH was 43.8±5.9%. After cessation of the somatostatin infusion there was a rise of plasma ACTH to starting levels within 1/2 hour. These findings suggest that somatostatin is a potent inhibitor of ACTH secretion, however, only in a condition in which glucocorticoids are lacking.
    Notes: Zusammenfassung Somatostatin (250 µg als Bolus i.v. und 250 µg als Dauerinfusion über eine Stunde) wurde 5 Patienten mit Nebennierenrindeninsuffizienz verschiedener Ätiologie gegeben. Bei jedem Patienten wurde ein anhaltender, kontinuierlicher Abfall des Plasma-ACTH während der Infusionsperiode beobachtet. Die durchschnittliche maximale Verminderung des Plasma-ACTH betrug 43,8±5,9%. Nach Beendigung der Somatostatininfusion stieg das Plasma-ACTH innerhalb einer halben Stunde wieder auf den Ausgangswert an. Diese Ergebnisse zeigen, daß Somatostatin ein potenter Inhibitor der ACTH-Sekretion ist, jedoch nur bei einem bestehenden Mangel an Glucokortikoiden.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 54 (1976), S. 717-725 
    ISSN: 1432-1440
    Keywords: Diabetes mellitus ; Pankreashormone ; Insulinantikörper ; Glukosetoleranztest ; Glibenclamide ; Diabetes mellitus ; Pancreatic Hormones ; Insulin Antibodies ; Glucose tolerance test ; Glibenclamide
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Human C-peptide is determined by radioimmunoassay. On gel filtration of serum from a healthy subject and from a patient with islet cell carcinoma, C-peptide (MW 3025) appears ahead of insulin (MW 5808) and shows much higher molar concentrations than the hormone. Human proinsulin cross-reacts with our antiserum to synthetic human C-peptide. On direct determination of immunomeasurable C-peptide (IMCP) in fasting serum of 25 healthy subjects we find an average of 1.8 (±0.4) ng/ml, corresponding to 60.4 × 10−11 Mol/l. The molar concentration is about five-fold as compared to IMI (immunomeasurable insulin). IMCP and IMI patterns are not identical on stimulation of beta-cell secretion in healthy subjects by i.v. glucose or glucose-glibenclamide. This is probably due to differences in peripheral metabolism of both compounds. We conclude from our results that C-peptide determined in peripheral venous serum is a better indicator of beta-cell secretion than is insulin. Among 26 insulin-treated juvenile diabetics 15 show not measurable and 11 subnormal IMCP levels in fasting serum. No rise in IMCP is found 1–2 h following breakfast. Four juvenile patients receiving no insulin in a phase of total diabetes remission have normal or raised fasting IMCP concentrations. Only 2 out of 24 adult diabetics (16 treated with insulin and 8 with tablets) show non-measurable fasting IMCP concentrations, in another 4 patients values are below and in the remaining 18 cases above 1 ng/ml serum. Stimulation of beta-cell secretion through glucoseglibenclamide is more or less impaired in all adult diabetics compared to the healthy subjects.
    Notes: Zusammenfassung Humanes C-Peptid wird radioimmunologisch bestimmt. Bei der Gelfiltration von Serum einer gesunden Probandin und einer Patientin mit Inselzellcarcinom erscheint C-Peptid (MG 3025) vor Insulin (MG 5808). Die molaren Konzentrationen für C-Peptid sind viel höher als für Insulin. Humanes Proinsulin reagiert mit unserem Antiserum gegen synthetisches humanes C-Peptid kreuz. Bei direkter Messung im Serum zeigen 25 Gesunde einen Nüchternspiegel für immunologisch meßbares C-Peptid (IMCP) von 1,8 (±0,4) ng/ml, entsprechend 60,4 × 10−11 Mol/l. Die molare Konzentration für immunologisch meßbares Insulin (IMI) beträgt ungefähr ein Fünftel dieses Wertes. Nach Stimulation der Beta-Zell-Sekretion mit i.v. Glukose oder Glukose-Glibenclamid finden sich bei Gesunden unterschiedliche Verl:aufe für IMCP und IMI. Wahrscheinlich erklärt sich dieser Befund mit einem unterschiedlichen peripheren Metabolismus beider Substanzen. Aus unseren Ergebnissen schließen wir, daß bei Messungen im peripheren venösen Serum C-Peptid ein besserer Indikator der Beta-Zell-Sekretion ist als Insulin. Von 26 insulinpflichtigen juvenilen Diabetikern zeigen 15 nicht meßbare und 11 subnormale IMCP Spiegel im Nüchternserum. 1–2 h nach dem Frühstück findet sich kein Anstieg für IMCP. Bei 4 juvenilen Diabetikern, die während einer totalen Remissionsphase ohne Insulin auskommen, liegen die IMCP Nüchternkonzentrationen im Normbereich für Gesunde oder darüber. Nur bei 2 von 24 erwachsenen Diabetikern (16 Fälle mit Insulin behandelt, 8 mit Tabletten) sind die IMCP Nüchternkonzentrationen nicht meßbar, bei 4 weiteren Patienten liegen sie unter, in den restlichen 18 Fällen dagegen über 1 ng/ml Serum. Die Stimulierbarkeit der Beta-Zell-Sekretion durch Glukose-Glibenclamid ist bei allen erwachsenen Diabetikern im Vergleich mit Gesunden mehr oder weniger eingeschränkt.
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 54 (1976), S. 977-982 
    ISSN: 1432-1440
    Keywords: Somatostatin ; Blutgerinnung ; Thrombozytenfunktion ; Somatostatin ; Blood coagulation ; Platelet function
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary The effect of short- and long-term somatostatin (GIF) administration on haemostatic function in man was investigated. The dosage programme applied in this study was 250 µg GIF as a bolus injection and 250 µg GIF/h by way of infusion. In five healthy volunteers a short-term (3 h) treatment resulted in a statistically significant drop of platelet count and impairment of platelet aggregation at the end of infusion. However, these changes were within the physiologically normal range and disappeared after two hours on all subjects. Other parameters such as bleeding time, thromboplastin and partial thromboplastin time, fibrinogen, fibrin/fibrinogen split products, plasma factor XIII, ethanol gelation test were not affected. In two patients with gastric haemorrhage and persistent amylasaemia a 67 or 120-h treatment induced no remarkable haemostatic defect. By contrast, peptic ulcer bleeding in one patient stopped 60 min after starting the GIF infusion. These studies indicated that somatostatin administration in man at the dosage programme used neither results in clinical evidence indicating bleeding tendency nor does it influence laboratory parameters in an apparent way.
    Notes: Zusammenfassung Die Beeinflussung verschiedener Haemostaseparameter beim Menschen durch Kurzund Langzeit-Anwendung von Somatostatin (GIF) wurde untersucht. Das in der Studie eingesetzte Dosierungsschema bestand aus einer intravenösen Bolusinjektion von 250 µg GIF und einer anschließenden Dauerinfusion von 250 µg GIF/h. Bei 5 gesunden, freiwilligen Probanden war nach Beendigung einer Kurzzeittherapie über 3 h ein statistisch signifikanter Abfall der Thrombozytenzahl und eine Beeinträchtigung der Thrombozytenfunktion nachweisbar. Die Veränderungen lagen jedoch innerhalb des physiologischen Normalbereiches und waren innerhalb von 2 h nach Infusionsende voll reversibel. Andere Parameter (Blutungszeit, Thromboplastinzeit und Partialthromboplastinzeit, Fibrinogen, Fibrinogen/Fibrinspaltprodukte, Blutgerinnungsfaktor XIII, Äthanoltest) wurden nicht beeinflußt. Bei 2 Patienten mit Magenblutung bzw. persistierender Amylasämie wurde die Somatostatin-Behandlung über 67 bzw. 120 h durchgeführt. Ein klinisch relevanter Haemostasedefekt war bei Therapieende labordiagnostisch nicht erkennbar. Im Fall des Patienten mit Magenblutung kam es vielmehr 60 min nach Beginn der Therapie zum Sistieren der Haemorrhagie. Die Untersuchungen haben gezeigt, daß nach Anwendung von Somatostatin beim Menschen unter Verwendung des angegebenen Dosierungsschemas weder klinische noch labordiagnostische Hinweise bestehen, die die Annahme einer klinisch relevanten, iatrogen-induzierten haemorrhagischen Diathese rechtfertigen.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 9 (1973), S. 135-139 
    ISSN: 1432-0428
    Keywords: Insulin secretion ; biosynthesis of proinsulin and insulin ; isolated pancreatic islets ; insulin content ; hypophysectomy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Insulin secretion and biosynthesis of proinsulin and insulin were determined in isolated pancreatic islets of hypophysectomized rats. Control rats were of both same age and weight. Hypophysectomy was performed either 13 or 5 weeks prior to the investigation, the weight of the animals being either 80 or 170 g. Biosynthesis of insulin was estimated from the amounts of radioactivity incorporated into proinsulin and insulin after incubation of isolated islets at 50 or 300 mg% glucose in the presence of3H-leucine for 3 h. Islet proteins were separated on Sephadex G 50 fine. — Hypophysectomy resulted in a significant decrease of both glucose stimulated secretion and biosynthesis of insulin. It was found that this reduction was 1) more significant when compared with controls of same age 2) more marked in rats which had been hypophysectomized 13 weeks before than in rats after an interval of 5 weeks and 3) less in rats which had been hypophysectomized at a weight of 170 g than in rats in whom pituitary ablation was performed at a weight of 80 g. At basal glucose concentrations, no significant changes of both secretion and biosynthesis of insulin were apparent. The relation of radioactivity incorporated into proinsulin and insulin was unchanged under all conditions. Insulin content of the isolated islets used was found within about the same range in all rats, apart from the animals which had been hypophysectomized 13 weeks before. In islets of these rats, a reduction to 84% was observed. — Our findings may be explained by reduced sensitivity of the pancreatic B-cell to glucose and a slower rate of insulin biosynthesis after hypophysectomy.
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 9 (1973), S. 140-144 
    ISSN: 1432-0428
    Keywords: Hypophysectomy ; growth hormone ; corticotrophin ; insulin secretion ; biosynthesis of proinsulin and insulin ; protein synthesis ; isolated pancreatic islets ; epiphyseal cartilage of the tibia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Hypophysectomized rats were substituted with varying doses of human or porcine growth hormone (GH) as well as with ACTH for 6 or 12 days. Hypophysectomy was performed in animals of 80 or 170 g body weight either 12 or 4 weeks prior to the onset of the therapy. Increase in weight and the width of the epiphyseal cartilage were determined, insulin secretion and biosynthesis of proinsulin and insulin, were investigated in isolated pancreatic islets of the animals. — No differences were found between the effects of human and poreine GH preparations. Weight gain was similar in rats which had been hypophysectomized at a weight of 80 g either 12 or 4 weeks prior to the substitution. Secretion and biosynthesis of insulin which were both found to be reduced in isolated islets of untreated, hypophysectomized rats, were improved or normalized after substitution with GH (1 mg/kg/day) for 12 days. On the other hand, a therapy with GH for 6 days, even in tenfold daily dose (10 mg/kg), was ineffective in all rats which had been hypophysectomized at a weight of 80 g. Normalisation of lowered levels of blood sugar was the only positive effect observed after an administration of ACTH for 6 or 12 days. — It appears from our findings that, in contrast to the administration of ACTH, GH given to hypophysectomized rats for a longer period in relatively low doses may normalize both reduced secretion and biosynthesis of insulin.
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  • 6
    ISSN: 1432-0428
    Keywords: Intestinal hormones ; isolated pancreatic islets ; insulin release
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé L'effet des hormones intestinales sécrétine, pancréozymine, gastrine-pentapeptide et glucagon sur la sécrétion d'insuline des ilôts pancréatiques isolés du rat a été étudié. Seule la pancréozymine et le glucagon se sont avérés stimuler la sécrétion d'insuline des ilôts isolés. La pancréozymine a produit cet effet sans glucose et le glucagon ne l'a produit qu'en présence de glucose dans le milieu. L'effet de la pancréozymine a été montré à plusieurs reprises en utilisant les même ilôts dans un système de perifusion dynamique. Ces études impliquent une classification des hormones intestinales, qui stimulent la sécrétion d'insuline selon que le tissu pancréatique exocrine intact est présent ou non.
    Abstract: Zusammenfassung Der Effekt der intestinalen Hormone Secretin, Pankreozymin, Gastrin-Pentapeptid und Glucagon auf die Insulinsekretion isolierter Langerhans'scher Inseln der Ratte wurde untersucht. Nur Pankreozymin und Glucagon stimulierten die Insulinsekretion der isolierten Inseln, Pankreocymin ohne, Glucagon nur bei Zusatz von Glucose zum Medium. Dieser Effekt von Pankreozymin war wiederholt an denselben Inseln in einem dynamischen Perifusionssystem nachzuweisen. Die Untersuchungen zeigen, daß die insulinstimulierende Wirkung der intestinalen Hormone zum Teil an ein funktionsfähiges exocrines Pankreasgewebe gebunden ist, zum Teil davon unabhängig zustande kommt.
    Notes: Summary The effect of the intestinal hormones secretin, pancreozymin, gastrin-pentapeptide and of glucagon upon insulin secretion of rat isolated pancreatic islets were studied. Only pancreozymin and glucagon were found to stimulate insulin release from the isolated islets, pancreozymin without and glucagon only in presence of glucose in the medium. The effect of pancreozymin was repeatedly shown by using the same islets in a dynamic perifusion system. The studies imply classification of the insulin stimulating actions of the intestinal hormones according to dependence upon and independence of the presence of intact exocrine pancreatic tissue.
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  • 7
    ISSN: 1432-0428
    Keywords: Oral antidiabetic agents ; sulphonylureas ; insulin response tests ; Glibenclamide ; prediction of long-term treatment ; formerly insulin-dependent maturity onset diabetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé Les auteurs dé crivent un nouveau test de réponse au sulfonylurée destiné à prévoir les résultats d'un traitement à long terme avec la Glibenclamide, composé sulfonylurée récent, particulièrement intéressant pour les diabétiques âgés, insulino-dépendants et ne réagissant pas à la tolbutamide. Le test est basé sur l'observation que la capacité du glucose à stimuler l'insuline et la détermination de l'augmentation de l'insuline sont fortement potentialisées après l'injection intra-veineuse de Glibenclamide plus glucose (25 γ plus 0.33 g/kg poids corporel). Les anticorps fixant l'insuline ont été extraits préalablement des échantillons de sérum. 11 diabétiques sur 40 montrant en moyenne plus de 500% d'accroissement d'insuline au-dessus des valeurs initiales, entre 60 et 90 mn. après l'injection, étaient en corrélation satisfaisante avec l'efficacité d'un traitement oral à long terme à la Glibenclamide. Le test positif de réponse à la Glibenclamide plus glucose a contrasté avec l'échec initial de la thérapeutique à la Glibenclamide chez un seul malade souffrant d'hémochromatose. Le traitement oral à la Glibenclamide peut avoir certains avantages sur la thérapeutique insulinique, particulièrement chez les diabétiques âgés souffrant de troubles visuels et ne pouvant s'injecter eux-mêmes l'insuline.
    Abstract: Zusammenfassung Ein neuer Sulfonylharnstoffvorhersagetest wird beschrieben. Er soll ermöglichen, das Ergebnis einer Langzeit-Therapie mit einem in letzter Zeit entwickelten Sulfonylhamstoffabkömmling (Gilben-clamid) besonders bei insulinpflichtigen, auf Tolbutamid nicht mehr ansprechbaren älteren Diabetiker vorauszusagen. Der Test beruht auf der Beobachtung, daß die insulinstimulierende Kapazität der Glucose und die Stärke des Insulinanstieges beträchtlich potenziert werden können, wenn Glibenclamid und Glucose zusammen gegeben werden (25 γ Glibenclamid plus 0.33 g/kg Körpergewicht Glucose). Das Insulin wurde bestimmt nach entsprechender Entfernung der insulinbindenden Antikörper. Von 40 Diabetikern zeigten 11 mehr als einen 500 prozentigen Insulinanstieg über den Ausgangswert zwischen der 60. und 90. Minute nach der Injektion. In diesen Fällen war der positive Test gut mit einer erfolgreichen Langzeittherapie korreliert. Nur bei einem Patienten mit Haemochromatose war trotz positivem Ausfall des Testes ein Versagen der Langzeit-Glibenclamidbehandlung zu beobachten. Die orale Therapie mit Glibenclamid hat gewisse Vorteile gegenüber der Insulintherapie, besonders bei älteren Patienten, die ein schlechtes Sehvermögen haben und daher unfähig sind, sich selbst Insulin zu spritzen.
    Notes: Summary A new sulphonylurea response test is described for predicting the results of long-term treatment with a recently developed sulphonylurea compound, glibenclamide, particularly in insulin-dependent tolbutamide-non-responsive elderly diabetics. The test is based on the observation that the insulin-stimulating capacity of glucose and the determination of the insulin increases are strikingly potentiated following glibenclamide plus glucose i.v. (25 γ plus 0.33 g/kg body weight) in serum samples where insulin binding antibodies have been removed. 11 out of 40 diabetics demonstrating between 60 and 90 min following injection, a mean increase of insulin of more than 500 per cent above the initial values, correlated satisfactorily with successful long-term oral treatment with glibenclamide. A positive glibenclamide-glucose-response test contrasted with primary failure of glibenclamide therapy in only one patient suffering from haemochromatosis. Oral treatment with glibenclamide may have certain advantages over insulin therapy, especially in elderly diabetics suffering from visual impairment, who are unable to inject themselves with insulin.
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  • 8
    ISSN: 1432-1440
    Keywords: Somatostatin ; Insulin ; C-peptide ; Diabetes ; Pituitary function ; Gastric acid secretion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A case of somatostatinoma syndrome in a 30-year-old woman is presented. Basal levels of growth hormone and of pancreatic and gastric hormones were reduced and the response of growth hormone, insulin and C-peptide to stimuli such as arginine, glucose, glibenclamide and calcium was virtually abolished. Similarly, gastric acid secretion, pancreatic exocrine function and intestinal absorption were significantly reduced. On the other hand, basal and stimulated levels of adrenocorticotropic hormone (ACTH), luteinizing hormone (LH), follicle-stimulating hormone (FSH) and thyroid-stimulating hormone (TSH) were within the normal range. Plasma somatostatin-like immunoreactivity was increased to 600 2,000 pg/ml (normal: 88–140 pg/ml). Immunocytochemical studies demonstrated the presence of somatostatin immunoreactive material in the primary tumour in the head of the pancreas and in the liver metastases. In spite of two courses of chemotherapy with streptozotocin and 5-fluorouracil the patient died due to liver failure 5 months after the first admission to hospital.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1433-8580
    Keywords: H2-Receptor ; Somatostatin ; Pancreatic polypeptide ; Gastrin ; Insulin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effect of histamine H2-receptor stimulation via the infusion of impromidine was assessed with regard to postprandial plasma insulin, pancreatic polypeptide (PP), somatostatin, and gastrin levels. The effect of impromidine was assessed in the postprandial state during a liver extract/sucrose test meal which had a buffer capacity to maintain the intragastric pH at a constant level for the time impromidine was infused. Postprandial plasma insulin and gastrin levels were not changed by impromidine (10µg/kg·h−1). Plasma somatostatin levels rose significantly, whereas the postprandial increase of plasma PP levels was attenuated. The effects on somatostatin and PP were antagonized by the infusion of cimetidine, a specific histamine H2-receptor blocker. In conclusion the present data demonstrate that in the postprandial state activation of H2-receptors stimulates somatostatin and inhibits PP release while insulin and gastrin release are not affected.
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