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  • 1
    ISSN: 1432-0428
    Keywords: Streptozotocin diabetes ; hypophysectomy ; rats ; hormonal replacement ; free and bound ribosomes ; protein synthesis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Acute insulin deficiency in rats results in a decrease in the in vitro protein synthetic activity of isolated hepatic membrane-bound ribosomes and an increase in activity of free ribosomes. These changes are prevented by concomitant insulin treatment and are reversed by the administration of insulin. The current study evaluated the role of the pituitary in the genesis of these changes. The severity of diabetes produced by streptozotocin was less in hypophysectomized (Hx) rats, and in Hx rats receiving hormone replacement, as compared with similarly streptozotocin-treated intact rats. Although acute insulin deficiency in intact rats produced the previously described increase in protein synthetic activity of free hepatic ribosomes and decrease in activity of hepatic bound ribosomes, these changes did not occur in Hx rats, even when Hx rats received replacement doses of thyroxine, ACTH, and growth hormone. Thus, the changes in hepatic protein synthetic activity that occur in rats with acute experimental diabetes mellitus are secondary to the metabolic sequelae of insulin lack and the response of the pituitary gland to insulin deficiency.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0428
    Keywords: Insulin deficiency ; protein synthesis ; hepatic ribosomes ; diabetic ribosomes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In order to define the effect of duration of diabetes on hepatic protein synthesis, membrane-bound and free ribosomes were isolated from livers of rats, 3, 7 and 28 days after administration of intravenous streptozotocin (75 mg/kg). Hepatocytes from the same rats were subjected to ultrastructural quantitative analysis. By day 3 there was a significant loss in the amount of rough endoplasmic reticulum (RER) per volume cytoplasm; however, the normal ratio of membrane-bound ribosomes per unit length of membrane was maintained. These hepatocyte ultrastructural changes continued over the ensuing four weeks. In spite of this decrease in amount of RER, in vitro protein synthetic activity of hepatic membrane-bound polyribosomes was unchanged from controls at three days, and by 28 days protein synthetic activity of bound hepatic ribosomes from diabetic rats was almost twice that of normal controls (p 〈.01). In contrast to the effect of diabetes on bound ribosomes, there was no change in protein synthetic activity of free polyribosomes isolated from livers of rats, 3, 7 or 28 days after induction of diabetes. Thus, the effect of any given degree of diabetes on hepatic protein synthesis appears to vary with the population of hepatic ribosomes being studied, and with duration of insulin deficiency.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-0428
    Keywords: Adrenaline ; glycogen metabolism ; glycolysis ; hexose monophosphates
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary There are important differences between the short- and long-term effects of adrenaline on determinants of glucose tolerance. To assess this metabolic adaptation at tissue level, the present study examined the effect of acute and prolonged in vivo elevation of adrenaline on glycogen metabolism and glycolysis in skeletal muscle. Adrenaline (50 ng · kg−1 · min−1) was infused for 2 h or 74 h and the results compared with 1 h 0.9% NaCl infusion in six trained dogs. Muscle glycogen content was reduced by long-term adrenaline (161 ± 17 vs NaCl 250 ± 24 μmol/g dry weight;p 〈 0.05) but not short-term adrenaline (233 ± 21) indicating a sustained effect of adrenaline on glycogen metabolism. Acutely, glycogen synthase I was reduced (short-term adrenaline 12 ± 6 vs NaC122 ± 7μmol glycosyl units · g−1 · min−1;p 〈 0.05) but returned to normal with prolonged adrenaline infusion (20 ± 5). In contrast, Km for glycogen phosphorylasea was not changed acutely (short-term adrenaline 31 ± 6 vs NaCl 27 ± 7 mmol/1 inorganic phosphate) but was reduced during long-term infusion (19 ± 4;p 〈 0.05 vs short-term adrenaline). Thus, with short- and long-term adrenaline infusion, there were different enzyme changes, although likely to promote glycogenolysis in both cases. In the glycolytic pathway the substrates glucose 6-phosphate and fructose 6-phosphate did not change significantly and hexokinase was not inhibited. Acutely, phosphofructokinase had reduced Vmax (short-term adrenaline 34 ± 6 vs NaCl 44 ± 5 U/g; p 〈 0.05) but was still above the maximal operating rate in vivo. With prolonged adrenaline infusion, the Km for phosphofructokinase was reduced (long-term adrenaline 0.32 ± 0.03 vs NaCl 0.44 ± 0.07 mmol/l fructose 6-phosphate;p 〈 0.05). In this situation of relatively low glycolytic flux, the sustained glycogenolytic effect of prolonged adrenaline infusion mediated by increased glycogen phosphorylase a ctivity occurs without a significant accumulation of hexose monophosphates or impairment of glycolysis.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 7 (1971), S. 173-180 
    ISSN: 1432-0428
    Keywords: Equivocal oral glucose tolerance ; intravenous glucose tolerance ; insulin tolerance tests ; immunoreactive insulin levels ; insulin sensitivity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé La tolérance intraveineuse au glucose, la libération d'insuline immuno-réactive et la réaction hypoglycémique à l'insuline exogène furent examinées chez neuf sujets normaux, chez quinze sujets diabétiques de l'âge adulte et chez vingt-cinq sujets (groupe équivoque) ayant une anomalie bénigne de la tolérance au glucose par voie orale (glucose à jeun 〈 110 mg% et des taux de deux heures 〈 170 mg%). La tolérance intraveineuse au glucose (K G.T.T.) et la sensibilité à l'insuline (K I.T.T.) du groupe équivoque allaient des valeurs normales à des valeurs peu élevées mais étaient nettement différentes des groupes normaux et franchement diabétiques. Dans le groupe équivoque, onze sujets eurent des valeurs normales, huit des valeurs diabétiques et six des valeurs limites deK G.T.T. Les réponses de l'insuline plasmatique dans le groupe équivoque eurent de grandes variations: sept réponses normales et dix-sept réponses typiquement diabétiques apparurent chez les individus ayant soit une tolérance normale au glucose intraveineux, soit une tolérance réduite. Malgré cette hétérogénéité, un diagnostic définitif fut établi chez onze des vingt-cinq sujets avec cette méthode d'enquête. — Des corrélations d'une signification positive furent démontrées à la fois entreK G.T.T. et l'insuline plasmatique et entreK G.T.T. et la sensibilité à l'insuline, suggérant que la tolérance complète au glucose dépend à la fois de la sensibilité envers l'insuline et de la quantité d'insuline plasmatique qui circule.
    Abstract: Zusammenfassung Die intravenöse Glucose-Toleranz, die Sekretion von immunreaktivem Insulin und die hypoglykaemische Reaktion auf exogenes Insulin wurde bei einer Reihe von Patienten untersucht: von diesen waren 9 normal, 15 hatten im reifen Alter einen Diabetes entwickelt, und 25 (eine Mittelgruppe) zeigten eine geringe Anomalie der oralen Glucose-Toleranz. (Blutzucker, nüchtern 〈 110 mg%, Werte nach 2 Std〈 170 mg%). Die Messung der intravenösen Glucose-Toleranz (K G.T.T.) und der Insulin-Empfindlichkeit (K I.T.T.) von Patienten in der Mittelgruppe ergaben normale oder niedrige Werte, aber sie waren deutlich verschieden von denen in der normalen oder diabetischen Gruppe. Innerhalb der Mittelgruppe hatten 11 Patienten normale, 8 diabetische und 6 GrenzlinienK G.T.T. Werte. — Die Anstiege des Plasma Insulins in der Mittelgruppe fielen sehr verschieden aus: 7 normale und 17 typisch diabetische Reaktionen fanden sich bei Patienten, die eine normale oder erniedrigte intravenöse Glucose-Toleranz hatten. Trotz dieser Unterschiede war es möglich, eine definitive Diagnose bei 11 der 25 Patienten mit Hilfe dieser Untersuchungsmethode zu stellen. — Signifikante positive Beziehungen wurden festgestellt zwischenK G.T.T. und Plasma Insulin einerseits undK G.T.T. und Insulin-Empfindlichkeit andererseits. Daraus folgt, daß die Gesamt-Glucose-Toleranz abhängig ist nicht nur von der Insulin-Empfindlichkeit, sondern auch von der Menge des Plasma-Insulins im Blutkreislauf.
    Notes: Summary Intravenous glucose tolerance, release of immunoreactive insulin and the hypog'lycaemic response to exogenous insulin were investigated in nine normal, fifteen maturity-onset diabetic and twenty-five subjects (equivocal group) with a mild abnormality of oral glucose tolerance (Fasting blood glucose 〈 110 mg%, and two hour levels 〈 170 mg%). — Intravenous glucose tolerance (-K G.T.T.) and insulin sensitivity (K I.T.T.) of subjects in the equivocal group ranged from normal to low values, but were significantly different from the normal and frank diabetic groups. Within the equivocal group, eleven subjects had normal, eight diabetic and six borderlineK G.T.T. values. — Plasma insulin responses within the equivocal group varied widely: seven normal and seventeen typical diabetic responses occurred in individuals with either normal or reduced intravenous glucose tolerance. Despite this heterogeneity, a definite diagnosis was established in eleven of the twenty-five subjects with the present method of investigation. — Significant positive correlations were demonstrated both betweenK G.T.T. and plasma insulin andK G.T.T. and insulin sensitivity, suggesting that overall glucose tolerance is dependent on both insulin sensitivity and on the amount of circulating plasma insulin.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-0428
    Keywords: Pancreatic-glucagon ; radioimmunoassay ; glucagon-free plasma ; glucagon-antibody coupled sepharose ; fasting levels ; normals ; diabetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Non-specific plasma effects may produce major errors in the estimation of true plasma pancreatic glucagon concentrations by radioimmunoassay. This has been circumvented by the production of glucagon-free plasma for each individual investigated, by means of glucagon antibody, coupled to sepharose beads. True fasting pancreatic glucagon levels (mean ± SEM) in 18 healthy subjects (24 ± 3 pg/ml) were significantly lower (p 〈 0.005) than in 10 non-ketotic non-obese diabetics (38 ± 3 pg/ml). It is suggested that, in the presence of decreased insulin-effect in the diabetic, this 55% glucagon elevation in diabetics may be of biological importance and contribute to the fasting hyperglycaemia.
    Type of Medium: Electronic Resource
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