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  • 1
    ISSN: 1432-0428
    Keywords: L-asparaginase ; glucose ; insulin ; glucose tolerance ; diabetes mellitus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary To study the effect of E. Coli L-asparaginase on glucose tolerance and insulin release, 6 patients with neoplastic disease were subjected to 3 hour oral glucose tolerance tests with simultaneous measurement of serum immunoreactive insulin (IRI) levels before and following the intravenous administration of 5000 I. U. L-asparaginase/day for 4 days. Five of the patients exhibited a significant deterioration in glucose tolerance; however, no change was noted in their fasting glucose and IRI levels. The deterioration in glucose tolerance was associated with a decrease in the amount of insulin secreted in the first 30 minutes after the oral glucose load. The total amount of insulin released during the 3 hour test remained unchanged. These studies suggest that L-asparaginase can cause a deterioration of glucose tolerance without accompanying fasting hyperglycaemia. This may be due, in part, to a decrease in glucose-induced insulin release during the first thirty minutes following oral glucose.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0428
    Keywords: Mice ; genetic selection ; fasting blood glucose ; body weight ; glucose tolerance ; insulin ; dietary fat ; isolated tissues ; randomfed
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Swiss-Hauschka mice have been selected for high (HG) and low (LG) fasting blood glucose (FBG) levels for four generations. All matings were brother to sister. Differences in mean FBG levels have remained relatively constant (20 to 30 mg%) between the two lines since initiation of selection (p〈0.001). Body weights have declined more rapidly with inbreeding in the LG line as compared to the HG line through F3, but no further decline was noted in the F4 generation. Fasting serum immunoreactive insulin (IRI) levels were variable and mean levels for the two lines did not differ significantly. A comparison of glucose tolerance data between F3 HG and LG line animals showed generally higher mean glucose levels in the HG line in both fasted and randomfed states. The mean delta glucose levels during the test, however, were nearly identical in both lines. A dietary influence on glucose tolerance was shown. Severalin vitro tissue studies revealed no significant differences in hepatic glycogen and pancreatic insulin content between HG and LG line animals. Isolated tissue sensitivity to insulin appeared indistinguishable between the lines; however, hepatic gluconeogenesis and retinal glucose-6-14C oxidation rates in HG line mice may be enhanced.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-0428
    Keywords: DBM mouse ; diabetic mutant mouse ; genotype: C57BL/Ks-db/db ; inherited diabetes ; diabetic heterozygote ; glucose tolerance ; serum insulin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé Des souris homozygotes et hétérozygotes porteurs du gène du diabète (db) ont été étudiées dans le but de déterminer: 1. si une intolérance latente aux hydrates de carbone existe chez la jeune sourisdbdb normoglycémique, 2. si la sourisdbdb normoglycémique ayant une alimentation réduite présente une intolérance aux hydrates de carbone, et 3. si la souris hétérozygote pour le gènedb (db/+) montre des anomalies de la tolérance au glucose, des taux d'IRI sériques et du poids corporel. Les taux de glucose sanguin ont été mesurés 0, 30, 60, 120 et 180 min après l'injection intrapéritoneale de 2 mg glucose/ gramme de poids corporel. Les souris normales (+/+) et diabétiques (db/db) ont des courbes de tolérance au glucose semblables au cours des 2 premières semaines de leur vie. Il apparaît pourtant qu'elles manifestent une intolérance marquée au glucose si on les compare avec la souris normale adulte. Un petit nombre de sourisdb/db âgées de 3 semaines présentent des glycémies plus élevées que celles observées chez les souris normales à la 180ème minute du test. A 4 semaines, la glycémie moyenne avant la charge glucosée (0 min) est significativement plus élevée (P〈 0.02) chez les animaux diabétiquesdb/db (144 mg glucose %) que chez la souris normale +/+ (124 mg glucose %). Bien que la réduction de nourriture diminue la glycémie à 0 min, l'intolérance au glucose est clairement manifeste après administration du glucose. Chez les animaux hétérozygotes (db/+) âgés de 3 à 16 mois, les anomalies de la tolérance au glucose sont surtout décélables chez les mâles qui montrent une élévation modérée mais statistiquement significative des taux de glucose sanguins à 0 min et après l'administration du glucose. 40% des mâles hétérozygotes ont des taux d'IRI sériques plus élevés que ceux mesurés chez les animaux mâles normaux. Le poids corporel des mâles hétérozygotes est significativement plus élevé (P〈0.01) que celui des mâles normaux du même âge.
    Abstract: Zusammenfassung In den vorliegenden Studien an homozygoten (db/db) und heterozygoten (db +) Mäusen des Diabetes-Stammes wurde untersucht: 1. ob bei den jungen, noch normoglykämischen homozygoten Tieren bereits eine Glucosetoleranz nachzuweisen sei; 2. ob Calorieneinschränkung die Glucosetoleranz homozygoter Tiere beeinflusse; und 3. ob bei heterozygoten Anomalien des Zuckerstoffwechsels nachweisbar seien. Bis zum Alter von zwei Wochen war die Glucosetoleranz homozygot diabetischer Tiere (db/db) derjenigen homozygot normaler Tiere (+/+) vergleichbar. In beiden Fällen war sie aber deutlich schlechter als bei normalen erwachsenen Mäusen. Ab der dritten Woche zeigten einige der künftig diabetischen Tiere gegenüber der Norm erhöhte 3-Stundenwerte. Im Alter von 4 Wochen war bei den diabetischen Tieren der Nullwert signifikant erhöht. Kalorienrestriktion beeinflußte die Glucosetoleranz nicht, obwohl die Blutzuckerkonzentration vor Belastung deutlich niedriger war als bei normal ernährten Tieren. Hétérozygote (db/+) Weibchen (3–16 Monate alt) waren völlig normal, während bei Männchen vor und nach Glucosebelastung signifikant erhöhte Blutzuckerkonzentrationen und, in 40% der Fälle, auch erhöhte Serum-IRI-Konzentrationen gemessen wurden. Das Körpergewicht männlicher Heterozygote war signifikant höher als dasjenige gleichaltriger Normaltiere.
    Notes: Summary Mice homozygous and heterozygous for the diabetes (db) gene were studied to determine: 1. whether latent carbohydrate intolerance is present in young normoglycemic diabetic mutants (db/db); 2. whether normoglycemic food restricted diabetic mutants are carbohydrate intolerant; and 3. whether mice heterozygous for thedb gene (db/+) manifest abnormalities in glucose tolerance, serum IRI levels or body weights. Blood glucose levels were determined 0, 1/2, 1, 2 and 3 h following intraperitoneal administration of 2 mg glucose/g body weight. Normals (+/+) and diabetics (db/db) showed similar glucose tolerance curves during the first two weeks of life; however, both were markedly glucose intolerant compared to normal adult mice. At 3 weeks a small number of mutants had higher 3 h levels than any achieved in normal mice. By 4 weeks the average value for diabetics prior to glucose loading (0 time) was significantly (P 〈 0.02) elevated (db/db — 144 mg glucose/100 ml, +/+ = 124 mg glucose/100 ml). Although food restriction reduced blood glucose concentration at 0 time, persistence of carbohydrate intolerance was readily demonstrable following glucose loading. — Abnormalities in heterozygotes (db/+), 3 to 16 months of age, were primarily restricted to male mice, which showed moderate, but statistically significant elevations in blood glucose both at 0 time and following glucose administration. Forty percent of male heterozygotes had higher serum IRI levels than any observed in normal control males. Body weights of male heterozygotes were significantly greater (P〈0.01) than those in agematched normals.
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  • 4
    ISSN: 1432-0428
    Keywords: Glucagonoma ; increased plasma “Large glucagon-immunoreactivity”
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Immunoreactive glucagon (IRG) fractions from plasma of 8 normal subjects and 4 patients with glucagon secreting tumors were studied by gel filtration techniques on Bio Gel P-30 and Sephadex G-50 columns. The pancreatic glucagon specific anti serum (30K) of Unger was utilized to measure IRG. Columns were calibrated with labelled albumin, proinsulin, insulin and glucagon. Four peaks were defined in normal and tumor bearing patients: peak I (〉20000 mol. wt.), peak II (primarily 9000 mol. wt.), peak III pancreatic glucagon (3500 mol. wt.) and peak IV small glucagon (〈3500 mol. wt.). Glucagonoma patients differed from our normal and reported normal subjects in that peak II contained most of the circulating IRG. The percent of IRG associated with peak II was 9.5–31.5% in normals and 39.1–61.2% in glucagonomas. Glucagon-like biological activity in an isolated hepatocyte system was demonstrated for all peaks. However, relative to immunoreactivity, peak II showed reduced activity (25–33%). Immunoassay of dilutions of all peaks revealed the probability of immuno determinants identical with porcine pancreatic glucagon. The presence of heterogeneous IRG peaks with biological glucagon-like activity suggest that the larger molecules may be prohormones. Further, it is possible that specific elevation of peak II may be a diagnostic feature of glucagonomas.
    Type of Medium: Electronic Resource
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