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  • 1
    ISSN: 1432-0428
    Keywords: Physical training ; glucose tolerance ; skeletal muscle glucose metabolism ; insulin sensitivity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effect of physical training on glucose tolerance in vivo and skeletal muscle glucose metabolism in vitro was investigated in normal rats. Treadmill running for 10 days up to 240 min/day led to a decrease of basal and glucose-stimulated plasma insulin levels without major alterations of the IV glucose tolerance (1 g/kg body weight). Swim training of two weeks' duration, i. e. exercise up to 2×75 min/ day, which did not induce significant changes in body composition, skeletal muscle glycogen levels or citrate synthase activity, resulted in a significant improvement of IV glucose tolerance and substantial reductions of basal and glucose-stimulated plasma insulin levels. Associated with this apparent improvement of insulin sensitivity in vivo, significant increases of the insulin-stimulated glucose uptake (+ 55%) and lactate oxidation (+ 78%) in vitro were found on perfusion of the isolated hindquarter of swim-trained animals. It is suggested that mild physical training can improve glucose tolerance and insulin sensitivity in normal rats, at least in part, due to an increase of insulin sensitivity of skeletal muscle glucose metabolism.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0428
    Keywords: Physical training ; obesity ; diabetes ; hypertriglyceridaemia ; glucose intolerance ; Zucker rat ; insulin resistance ; perfused hindquarter
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effect of treadmill training on intravenous glucose tolerance and insulin sensitivity was investigated in Zucker rats (fafa). In 25-week-old fafa animals with the typical metabolic syndrome of massive obesity, glucose intolerance, hypertriglyceridaemia and insulin resistance, treadmill exercise of only very mild intensity was carried out for 6 weeks. The training programme induced a marked reduction in basal and post-glucose challenge plasma insulin levels and a slight but significant improvement of intravenous glucose tolerance. No alteration in insulin sensitivity of the isolated perfused hindquarter was demonstrable. In another study a 9-week training programme was started in 7-week-old fafa rats before the development of their metabolic syndrome. In the sedentary control animals glucose intolerance and insulin resistance developed during the study period; in the training group, both the deterioration of glucose tolerance and the decrease of insulin sensitivity were prevented. This study demonstrates in fafa rats that (a) in young animals physical training may prevent a genetically predisposed deterioration of glucose tolerance and insulin sensitivity and (b) in adult animals mild physical training may improve intravenous glucose tolerance and insulin sensitivity.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-0428
    Keywords: Type 1 (insulin-dependent) diabetes mellitus ; autoimmunity ; T cells ; rat insulinoma (RIN) tissue
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Type 1 (insulin-dependent) diabetes mellitus is a T-cell mediated autoimmune disease with a number of different proteins being implicated as target autoantigens. A 38 kDa protein residing in the insulin secretory granule of insulinoma tissue is recognized by T-cell clones from a newly-diagnosed Type 1 diabetic patient. We have investigated the capacity of normal rat pancreatic beta-cell extracts and various subcellular fractions of transplantable RIN tissue to induce proliferation of T cells from non-obese diabetic (NOD) mice and H-2 identical NON · NOD-H-2g7 control mice. Normal rat islet beta-cell protein fractions induced intense, dose-dependent proliferation of NOD splenic T cells, but only marginal proliferative responses of NON · NOD-H-2g7 splenic T cells. To further localize the target antigens, four different subcellular fractions from RIN tissue were used as a source of antigen; here in particular the cytosolic proteins showed dose-dependent activation capacity with splenic T cells in NOD animals. These activities were absent in control mice. There was no proliferation after incubation with microsome preparations from other rat endocrine tissues. Purified carboxypeptidase H did not have any stimulatory activity on NOD T cells. Fractionation of the RIN cytosolic proteins showed a large number of different fractions eliciting proliferative activity. These results demonstrate that NOD T cells respond to a large number of potential islet beta-cell target antigens and it will be necessary to utilize NOD T-cell clones to identify the number and nature of these antigens.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-0428
    Keywords: Free fatty acids ; glucose tolerance ; pregnancy ; potential diabetes ; symptoms of potential diabetes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé 97 femmes entre 18 et 52 ans ont été soumises à un test de tolérance glucidique par voie intraveineuse avec injection de 25 g de glucose (50 ml d'une solution de 50%). Les concentrations du glucose sanguin et des acides gras libres (AGL) ont été déterminées avant (à jeun) et 10, 20, 40 et 60 min après injection du glucose. — 49 des 97 femmes examinées étaient enceintes, tandis que 48 ne l'étaient pas. Chacun des deux groupes était composé d'un groupe de contrôle normal, d'un groupe de femmes avec prédisposition génétique au diabète, d'un autre présentant des symptômes obstétriques et gynécologiques d'un diabète potentiel (naissance d'un enfant mort inexpliqué, naissance d'un ou plusieurs enfants de poids excessif) et d'un groupe de femmes obèses. — On constate que la chute des AGL est déjà retardée chez les personnes de contrôle enceintes sans anomalie métabolique apparente. A tous les intervalles examinés ces valeurs sont significativement plus élevées chez ces femmes que chez les personnes de contrôle non-enceintes. La présence de symptômes d'un diabète potentiel n'influence pas la chute des AGL après injection i.v. de glucose, même si on considère le collectif. D'autre part, chez des femmes nonenceintes avec diabète potentiel, nous avons démontré des différences significatives de la chute des AGL dans 2 des 3 groupes examinés par comparaison avec le groupe normal de contrôle. — Ces résultats indiquent que les taux élevés des AGL constatés à tous les intervalles examinés et leur chute retardée après surcharge intraveineuse chez les femmes enceintes normales sont dus à une hormone placentaire avec action lipolytique, telle qu'elle a été décrite dans la littérature [4, 33, 34]. — Il existe donc une lipolyse exagérée chez des femmes enceintes sans autre anomalie métabolique. Dans ce sens, une grossesse exerce un effet diabétogène indirect. La présence simultanée d'un diabète potentiel pendant la grossesse ne mène pas à d'autres modifications mesurables de la chute des AGL. — L'augmentation physiologique de la lipolyse ne permet pas de démontrer la diminution de la lipogénèse à laquelle on s'attendrait chez ces femmes à cause du manque relatif d'insuline à effet normal. Pour cette raison, la mesure des taux des AGL sous surcharge glucidique intraveineuse pendant la grossesse n'est pas indiquée pour le dépistage des états prédiabétiques.-En dehors de la grossesse et en présence des symptômes indiqués ci-dessus, on peut démontrer un manque relatif d'insuline à action normale par la chute retardée des AGL en comparaison avec le groupe normal de contrôle. En conséquence, les mesures des taux des AGL sous surcharge glucidique intraveineuse pour le dépistage des états prédiabétiques ne sont indiquées qu'en dehors de la grossesse.
    Abstract: Zusammenfassung Bei 97 Frauen im Alter zwischen 18 und 52 Jahren wurde eine intravenöse Glucosebelastung mit Injektion von 25 g Glucose (50 ml einer 50%igen Lösung) durchgeführt. Vor (nüchtern) und unter (10, 20, 40 und 60 Min. nach Injektion der Glucose) der Belastung wurde gleichzeitig die Konzentration des Blutzuckers und der freien Fettsäuren bestimmt. — Von den untersuchten 97 Frauen waren 49 gravide und 48 außerhalb der Schwangerschaft. Diese beiden Gruppen setzten sich jeweils aus einer gesunden Kontrollgruppe, aus einer Gruppe von Frauen mit genetisch diätetischer Belastung, einer anderen mit geburtshilflich-gynäkologischen Symptomen eines potentiellen Diabetes (ungeklärte Totgeburt, Geburt eines oder mehrerer Riesenkinder) und aus je einer Gruppe mit fettleibigen Frauen zusammen. — Es zeigt sich, daß der Abfall der freien Fettsäuren schon bei vermutlich stoffwechselgesunden graviden Kontrollpersonen insgesamt verzögert ist. Die einzelnen Werte sind zu allen Bestimmungszeiten bei graviden gesunden Kontrollpersonen statistisch signifikant höher als bei nicht graviden Kontrollpersonen. Das gleichzeitige Vorliegen von Symptomen eines potentiellen Diabetes (genetisch diabetische Belastung, ungeklärte Totgeburten, die Geburt eines oder mehrerer Riesenkinder oder eine Fettleibigkeit) verändert den Abfall der freien Fettsäuren nach intravenöser Glucosegabe auch im Kollektiv nicht. Außerhalb der Gravidität fand sich dagegen bei Patientinnen mit Symptomen eines potentiellen Diabetes in zwei von drei untersuchten Gruppen ein statistisch signifikanter Unterschied im Abfall der freien Fettsäuren im Vergleich zur gesunden Kontrollgruppe. — Diese Befunde lassen sich dahingehend deuten, daß die zu allen Entnahmezeiten erhöht gefundenen Konzentrationen der freien Fettsäuren und der verzögerte Abfall dieser Werte nach intravenöser Glucosebelastung bei gesunden schwangeren Frauen durch ein lipolytisch wirksames Hormon der Placenta bedingt ist, wie das in der Literatur beschrieben wurde [4, 33, 34]. —Es besteht somit bei stoffwechselgesunden Graviden eine erhöhte Lipolyse. Eine Schwangerschaft könnte in diesem Sinne indirekt diabetogen wirken. Das gleichzeitige Auftreten von Symptomen eines potentiellen Diabetes bedingt keine weiteren nachweisbaren Veränderungen im Abfall der freien Fettsäuren in der Schwangerschaft. Die schon physiologischerweise erhöhte Lipolyse läßt eine verminderte Lipogenese, die bei solchen Patientinnen infolge relativen Mangels an wirksamem Insulin zu erwarten wäre, nicht mehr nachweisen. Bestimmungen der Konzentration der freien Fettsäuren während intravenöser Glucosebelastung sind daher innerhalb einer Gravidität für die Erfassung frühdiabetischer Zustände nicht geeignet.-Außerhalb der Gravidität kann demgegenüber bei Vorliegen der oben genannten Symptome ein relativer Mangel wirksamen Insulins aufgrund des verzögerten Abfalls der freien Fettsäuren gegenüber der gesunden Kontrollgruppe vermutet werden. Bestimmungen der Konzentration der freien Fettsäuren nach intravenöser Glucosebelastung sind daher nur außerhalb einer Schwangerschaft zur Erfassung frühdiabetischer Zustände sinnvoll.
    Notes: Summary In 97 women (aged 18–52 years) blood glucose and nonesterified fatty acids were determined before and following a rapid intravenous injection of 25 g glucose (50 ml, 50% solution). 49 of these women were pregnant. For the two main groups (pregnant and nonpregnant), women were selected if they fulfilled one of the following criteria: 1. normal weight without signs of metabolic disorders (control persons); 2. a positive family history of diabetes; 3. history of unexplained perinatal mortality or previous delivery of an infant weighing 4500 g or more; 4. obesity without signs of metabolic disorders. — We found that the slope of the free fatty acids was retarded in pregnant controls. The blood levels of the free fatty acids were always significantly higher than in nonpregnant controls. We even found the same slope of the free fatty acids following an intravenous glucose tolerance test in pregnant women with the above mentioned criteria. In the main group of non-pregnant women with a family history of diabetes or the other diabetic signs, we found a statistically significant difference in the slope of the free fatty acids in 2 of the 3 groups tested compared with controls without metabolic disorders. — These results imply that the raised level of the free fatty acids and the delayed slope following an intravenous glucose tolerance test in healthy pregnant women are due to a lipolytic effect of a placental hormone as already published [4, 23, 34]. — These findings apply to an elevated lipolysis in healthy pregnant women. Thus pregnancy may have an indirect diabetogenic effect. The reduced lipogenesis, caused by the relative deficiency of insulin in pregnant women with familial history of diabetes, cannot be verified since lipolysis is physiologically raised in pregnancy. During pregnancy the determination of free fatty acids following in intravenous glucose tolerance test is not available for the exact diagnosis of a diabetic metabolism. In non-pregnant women with the symptoms above mentioned, the reduced lipogenesis caused by the relative insufficiency of effective insulin would be verified by the delayed slope of free fatty acids. — Therefore the determination of the concentration of the free fatty acids following an intravenous glucose tolerance test is useful only in non-pregnant women for the diagnosis of latent diabetes.
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  • 5
    ISSN: 1432-0428
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-0428
    Keywords: Key words Zucker rats, skeletal muscle, insulin resistance, glucose transporter (GLUT 1 and GLUT 4), GLUT 4 translocation.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The genetically obese Zucker rat (fa/fa) is an animal model with severe insulin resistance of the skeletal muscle. We investigated whether a defect of insulin-dependent glucose transporter (GLUT 4) translocation might contribute to the pathogenesis of the insulin-resistant state. fa/fa rats, lean controls (Fa/Fa) as well as normal Wistar rats were injected intraperitoneally with insulin and were killed after 2 or 20 min, respectively. Subcellular fractions were prepared from hind-limb skeletal muscle and were characterized by determination of marker-enzyme activities and immunoblotting applying antibodies against α1 Na+/K+ AT Pase. The relative amounts of GLUT 1 and GLUT 4 were determined in the fractions by immunoblotting with the respective antibodies. Insulin induced an approximately two-fold increase of GLUT 4 in a plasma membrane and transverse tubule enriched fraction and a decrease in the low density enriched membrane fraction in all three groups of rats. There was a high individual variation in GLUT 4 translocation efficiency within the groups. However, no statistically significant difference was noted between the groups. No effect of insulin was detectable on the distribution of GLUT 1 or α1 Na+K+ AT Pase. The data suggest that skeletal muscle insulin resistance of obese Zucker rats is not associated with a lack of GLUT 4 translocation. [Diabetologia (1994) 37: 3–9]
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  • 7
    ISSN: 1432-0428
    Keywords: Zucker rats ; skeletal muscle ; insulin resistance ; glucose transporter (GLUT 1 and GLUT 4) ; GLUT 4 translocation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The genetically obese Zucker rat (fa/fa) is an animal model with severe insulin resistance of the skeletal muscle. We investigated whether a defect of insulin-dependent glucose transporter (GLUT 4) translocation might contribute to the pathogenesis of the insulin-resistant state. fa/fa rats, lean controls (Fa/Fa) as well as normal Wistar rats were injected intraperitoneally with insulin and were killed after 2 or 20 min, respectively. Subcellular fractions were prepared from-hind-limb skeletal muscle and were characterized by determination of marker-enzyme activities and immunoblotting applying antibodies against α1 Na+/K+ AT Pase. The relative amounts of GLUT 1 and GLUT 4 were determined in the fractions by immunoblotting with the respective antibodies. Insulin induced an approximately two-fold increase of GLUT 4 in a plasma membrane and transverse tubule enriched fraction and a decrease in the low density enriched membrane fraction in all three groups of rats. There was a high individual variation in GLUT 4 translocation efficiency within the groups. However, no statistically significant difference was noted between the groups. No effect of insulin was detectable on the distribution of GLUT 1 or α1 Na+K+ ATPase. The data suggest that skeletal muscle insulin resistance of obese Zucker rats is not associated with a lack of GLUT 4 translocation.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1432-0428
    Keywords: Keywords Leptin ; ob gene ; gene expression ; insulin resistance ; obesity.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Increased levels of mRNA transcribed from the ob gene in adipose tissue of obese/hyperinsulinaemic Zucker (fa/fa) rats were detectable as early as 3 weeks after birth and continued to rise there after in parallel with body weight and serum insulin. mRNA levels of two other fat-specific genes (ARL4, FST44) were unaltered. In C57BL/KsJ db/db mice, ob mRNA levels also increased in parallel with body weight and serum insulin, and remained elevated in older animals when insulin levels decreased. In heterozygous control animals (db/ + ; fa/Fa), mRNA levels were comparable with those in the homozygous controls. In normal Sprague Dawley rats, the ob mRNA increased continuously, but more slowly than in Zucker rats, in parallel with body weight and insulin levels, and reached 15 times higher levels in the heaviest rats (400 g) studied. In Sprague Dawley rats made diabetic by an injection of streptozotocin, ob mRNA levels were reduced by approximately 50 % after 24 h. A 24-h fasting period reduced the ob mRNA by 50 % in lean Sprague Dawley and Fa/Fa, but not in obese Zucker fa/fa rats, although insulin levels were reduced in both groups. These data indicate that ob mRNA levels increase in both normal and obese rodents in parallel with age, body weight and serum insulin, reflecting an early (Zucker rats, db-mice) or slowly developing (Sprague Dawley rats) resistance to leptin and insulin. This increase does not appear to be mediated by the recently described rapid regulation of ob mRNA by insulin, but seems to be due to a different, long-term control mechanism which signals the size of the fat depots. [Diabetologia (1996) 39: 758–765]
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  • 9
    ISSN: 1432-0428
    Keywords: Spontaneous diabetes ; mutationobob ; NZO mice ; diabetes in mice ; obesity in mice ; hereditary obesity ; adipose tissue ; lipolysis ; lipogenesis ; size of fat cells
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé Chez la souris NZO, il existe une étroite corrélation entre la dimension de la cellule adipeuse et l'augmentation du poids corporel. Chez ces animaux, la libération des AGL et du glycérol à partir du tissu adipeux augmente en fonction du poids et de la dimension des cellules adipeuses, que ce soit dans les conditions de base ou après stimulation par la noradrénaline, l'ACTH, le DB-AMP cyclique et la théophylline. La réponse aux agents lipolytiques est la même chez la souris NZO normopondérale et les souris normales provenant de la même nichée que les sourisobob. Chez ces dernières, la dimension de la cellule adipeuse et le poids corporel sont en corrélation jusqu'à un poids corporel d'environ 60 g. Chez des sourisobob plus âgées, une diminution de la dimension de la cellule est observée lorsque le poids augmente. Aucune corrélation ne peut être établie entre la stimulation de la lipolyse et la dimension de la cellule adipeuse. Il existe une corrélation inverse entre l'insulinémie et la stimulation de lipolyse dans le tissu adipeux. — Il est conclu de ces expériences que les souris NZO pourraient être atteintes d'un type d'obésité hypértrophiqué et les souris obob d'un type d'obésité hyperplasique, dont la distinction semble pouvoir se faire par l'examen morphologique de la cellule adipeuse et par la sensibilité du tissu adipeux aux agents lipolytiques.
    Abstract: Zusammenfassung BeiNZO-Mäusen besteht eine enge Korrelation zwischen Zunahme des Körpergewichtes und Vergrößerung der Einzelfettzelle. Unter Basalbedingungen sowie nach Stimulierung mit Noradrenalin, ACTH, DB-cyclo AMP und Theophyllin nimmt die Freisetzung von Glycerin und freien Fettsäuren aus dem Fettgewebe beiNZO-Mäusen mit steigendem Körpergewicht und Vergrößerung der Fettzelle zu. — Junge, nicht fettsüchtigeNZO-Mäuse und nicht fettsüchtige Wurfgeschwister hyperglykämischerobob-Mäuse reagieren in ähnlicher Weise auf lipolytische Stimuli. — Beiobob-Mäusen besteht zwischen der Fettzellgröße und dem Körpergewicht eine Korrelation, bis die Tiere ein Gewicht von ungefähr 60 g erreicht haben. Bei älterenobob-Mäusen tritt trotz einer weiteren Zunahme des Körpergewichtes eine Abnahme der Fettzellgröße auf. Es besteht keine Korrelation zwischen stimulierter Lipolyse und Fettzellgröße. Die Höhe des Seruminsulinspiegels und die stimulierte Lipolyse des Fettgewebes verhalten sich bei diesen Tieren umgekehrt proportional. — Es wird geschlossen, daßNZO-Mäuse den Typ einer hypertrophischen Fettsucht undobob-Mäuse den Typ einer hyperplastischen Fettsucht verkörpern, die sich hinsichtlich der Fettzellmorphologie und der Empfindlichkeit des Fettgewebes auf lipolytische Agenzien voneinander unterscheiden.
    Notes: Summary In NZO mice fat cell size is strongly correlated to increasing body weight; FFA and glycerol release from adipose tissue under basal conditions and after stimulation with norepinephrine, ACTH, DB-cyclic AMP and theophylline increase with body weight and fat cell size. Normal weight NZO mice and lean littermates ofobob mice respond similarly to lipolytic agents. — Inobob mice cell size and body weight are correlated until a body weight of about 60 g is reached. Olderobob mice show a decrease in cell size with increasing body weight. There is no correlation between stimulated lipolysis and fat cell size. In these animals an inverse relationship between serum insulin and stimulated lipolysis in adipose tissue was observed. — It is concluded that NZO mice exhibit a type of hypertrophic obesity andobob mice a type of hyperplastic obesity, which may be differentiated by fat cell morphology and the sensitivity of adipose tissue to lipolytic agents.
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  • 10
    ISSN: 1432-0428
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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