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  • isolated pancreatic islets  (3)
  • Diabetes mellitus  (2)
  • Euglycaemic clamp  (2)
  • 1
    Electronic Resource
    Electronic Resource
    Characterization of insulin resistance in type I diabetes (1985)
    Springer
    Journal of molecular medicine 63 (1985), S. 545-553 
    Details
    ISSN: 1432-1440
    Keywords: Type I diabetes ; Insulin resistance ; Euglycaemic clamp ; Insulin receptor binding ; Insulin antibodies
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Insulin sensitivity was assessed using the euglycaemic clamp technique in eight type I diabetic patients (after overnight blood glucose normalization with an artificial pancreas) and in six healthy subjects. Basal insulin concentrations were higher in diabetic patients (25±4 µU/ml) than in control subjects (17±1 µU/ml;P〈0.05). Insulin infusion of 0.5, 1.0, 2.0 and 5.0 mU/kg per min during subsequent 2-h periods resulted in similar mean steady-state insulin concentrations in both groups. The mean dextrose requirements during the last 40 min of each period were nevertheless decreased in diabetic patients (1.6±0.5, 3.5±0.8, 6.5±0.7, 10.2±0.7 mg/kg per min) as compared with control subjects (4.7±0.3, 8.2±0.9, 10.2±0.9, 12.4±0.9 mg/kg per min). At low insulin concentrations dextrose requirements were diminished in all diabetic subjects. At the highest insulin levels, individual dose-response curves from only four patients were within the normal range. Under basal conditions, the monocyte receptor number was significantly reduced in diabetic patients (17,500±2,800 sites/cell) as compared with control subjects (26,700±2,500 sites/cell;P〈0.05), whereas there were no differences regarding empty site affinities. Receptor data did not differ in patients with normal and decreased maximal dextrose requirements. Insulin resistance is apparently a common feature of type I diabetes at serum insulin concentrations of approximately 100 µU/ml. Normalization of the insulin effect by higher insulin concentrations is not possible in all patients. Insulin antibodies at concentrations observed in this study (〈0.16 mU/ml) do not contribute significantly to insulin resistance; receptor and postreceptor defects are possibly more important.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01733199
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  • 2
    Electronic Resource
    Electronic Resource
    Semisynthetic human insulin and purified pork insulin do not differ in their biological potency (1984)
    Springer
    Journal of molecular medicine 62 (1984), S. 1145-1150 
    Details
    ISSN: 1432-1440
    Keywords: Semisynthetic human insulin ; Biological potency ; Insulin hypoglycaemia ; Euglycaemic clamp
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The biological potency of semisynthetic human insulin (Actrapid HM, Novo) and purified pork insulin (Actrapid MC, Novo) was assessed in normal and diabetic subjects. The blood glucose lowering effect and the related counter-regulatory response were initially tested in six healthy subjects who received an i.v. injection of 0.15 U/kg body weight of either insulin preparation. The attained insulin levels were very similar (peak at 15 min: HM 139±7, MC 129±7 µU/ml), as well as the resulting blood glucose curves. A prolonged suppression of C-peptide values was observed after injecting both preparations. The evoked counter-regulatory response [glucagon, growth hormone (GH), cortisol and catecholamines] showed minimal differences. Prolactin secretion was almost identical after HM and MC injection. A glucose clamp study was subsequently performed in six insulin-dependent diabetic (IDD) patients. Blood glucose levels were maintained at 80 mg/dl by the artificial pancreas during a 180 min infusion of MC or HM insulin (30 mU/kg/h). The amounts of dextrose infused during the last 60 min of the study were not significantly different (121±14 vs 137±11 mg/kg/h for MC and HM, respectively). It is clear from our results that at the dose levels used in this study, the biological potency of i.v. injected HM is very similar to that of MC.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01712180
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  • 3
    Electronic Resource
    Electronic Resource
    Hypophysis and function of pancreatic islets (1973)
    Springer
    Diabetologia 9 (1973), S. 135-139 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01230693
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  • 4
    Electronic Resource
    Electronic Resource
    Hypophysis and function of pancreatic islets (1973)
    Springer
    Diabetologia 9 (1973), S. 140-144 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01230694
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  • 5
    Electronic Resource
    Electronic Resource
    The role of the exocrine pancreas in the stimulation of insulin secretion by intestinal hormones (1971)
    Springer
    Diabetologia 7 (1971), S. 1-5 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02346246
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  • 6
    Electronic Resource
    Electronic Resource
    Human C-peptide (1976)
    Springer
    Journal of molecular medicine 54 (1976), S. 717-725 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01470463
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  • 7
    Electronic Resource
    Electronic Resource
    Humanes C-Peptid (1978)
    Springer
    Journal of molecular medicine 56 (1978), S. 111-120 
    Details
    ISSN: 1432-1440
    Keywords: C-peptide ; Diabetes mellitus ; Glibenclamide, therapeutic use ; Insulin secretion ; C-Peptid ; Diabetes mellitus ; Glibenclamid, therapeutische Anwendung ; Insulinsekretion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Erwachsene Diabetiker wurden je nach Therapie vor und nach einem Behandlungsversuch mit Diät und Glibenclamid in 4 Gruppen eingeteilt: I: vorher Insulin — nachher Insulin, II: Tabletten — Insulin, III: Insulin — Tabletten und IV: Tabletten — Tabletten. Bei 6 Stoffwechselgesunden und 10 Patienten aus jeder Diabetikergruppe wurde die Sekretionskapazität der Beta-Zellen nach i.v. Belastung mit Glibenclamid-Glukose mittels C-Peptid Messungen untersucht. Bei den Diabetikern aller Gruppen kam eine Sekretionsstarre in einem verminderten und verzögerten Anstieg von immunologisch meßbarem C-Peptid (IMCP) zum Ausdruck. Bei tablettenbedürftigen Patienten hielt die Sekretion allerdings länger an als bei Stoffwechselgesunden. Im Mittel waren der Zuwachs von IMCP und die integrierten Stimulationsflächen bei tablettenbedürftigen Patienten (III+IV) viel größer als bei insulinbedürftigen (I+II). Eine Varianzanalyse wurde für die insulinbedürftigen Fälle einerseits und die tablettenbedürftigen Patienten andererseits durchgeführt. Die Gruppen I und II unterscheiden sich überzufällig bezüglich der Gruppenmittelwerte für IMCP, während der zeitliche Verlauf der IMCP Mittelwerte der beiden Gruppen nur zufällig von der Parallelität abweicht. In den Gruppen III und IV unterscheiden sich weder die Gruppenmittelwerte überzufällig, noch konnte eine Abweichung der jeweiligen zeitlichen Verläufe von der Parallelität nachgewiesen werden. Der zeitliche Verlauf konnte für Insulinbedürftige durch ein Regressionspolynom 2. Grades, für Tablettenbedürftige durch ein Regressionspolynom 4. Grades dargestellt werden. Die Kurven unterscheiden sich erheblich in Ausmaß und Steilheit ihres Anstiegs. Die Therapievorhersage nach i.v. Belastung mit Glibenclamid-Glukose, die bisher auf Kriterien des Blutglukoseverlaufs beruhte, ist bei Kenntnis des IMCP Verlaufs leichter und zuverlässiger möglich. Als natürlicher Verlauf des Diabetes mellitus im Erwachsenenalter ist die Entwicklung der Restsekretion der Beta-Zellen vom Stadium der Gruppen III und IV über Gruppe II zum Stadium der Gruppe I wahrscheinlich.
    Notes: Summary Adult diabetics were divided into 4 groups according to therapy before and after a therapeutic trial with diet and glibenclamide: I: insulin before — insulin afterwards, II: tablets — insulin, III: insulin — tablets and IV: tablets — tablets. The secretion capacity of the beta-cells, determined by C-peptide was examined in 6 healthy subjects and in 10 diabetics of each group following an i.v. glibenclamide-glucose load. A decreased insulinogenic reserve showing itself in a reduced and delayed rise of immunomeasurable C-peptide (IMCP) was found in all diabetics. However, the secretion of IMCP lasted longer in the diabetics requiring tablets than in the healthy subjects. The average values for the increment of IMCP and the integrated stimulation areas were much more considerable in the patients treated with tablets (III+IV) than in the insulin-dependent patients (I+II). An analysis of variance was performed for the diabetics depending on insulin, on the one hand, and the patients depending on tablets on the other. Between groups I and II the group average values for IMCP are significantly different while differences in the time course of the IMCP mean values of both groups are accidental. Neither the group average values of IMCP nor the time course of the IMCP mean values show significant differences between groups III and IV. The time course of IMCP was described by a regression polynomial of 2nd degree in insulin-dependent diabetics and a polynomial of 4th degree in diabetics depending on tablets; the corresponding curves differ considerably as to extent and steepness of their rise. Prediction of suitable diabetes therapy from an i.v. glibenclamide-glucose load based on blood glucose evaluation up to now is easier and more reliable since C-peptide levels are known. A development of the residual beta-cell function from the stage in groups III and IV via group II to the stage in group I is likely to be the natural course of adult diabetes.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01478566
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