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  • 1
    ISSN: 1432-0428
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé 1. Un cas de diabète insulino-résistant est présenté en détail et l'attention attirée sur le rapport chronologique entre le début du diabète et une série de traitements antérieurs à l'insulino-choc. 2. Les anticorps anti-insuline ont été localisés dans les γ-globulines par l'emploi consécutif d'électrophorèse et de filtration sur Sephadex. La majorité des anticorps anti-insuline s'est révélée être des globulines γg, avec un débordement important sur la région des globulines γa. 3. La relation pathogénique possible entre la réaction immunologique de la malade et la manifestation du diabète est considérée.
    Abstract: Zusammenfassung 1. Ein Fall von insulinresistentem Diabetes mellitus bei einer Patientin wird ausführlich beschrieben. Das Verhältnis zwischen einer früheren Insulinbehandlung aus psychiatrischer Indikation und dem späterem Auftreten von manifestem Diabetes wird besonders berücksichtigt. 2. Die Lokalisierung der Insulinantikörper in der γg-Globulinfraktion mit Übergang auf die γa Fraktion wird beschrieben. 3. Der mögliche Zusammenhang zwischen der Immunisierung der Patientin und dem Manifestwerden der Krankheit wird diskutiert.
    Notes: Summary 1. A patient with insulin resistant diabetes mellitus has been described in detail with emphasis upon the time relationship between prior insulin therapy for mental illness and the subsequent development of overt diabetes. 2. The localization of the insulin antibodies in the γg-globulins with some extension into the region of γa has been delineated. 3. The possible relationship between the immunologic responsiveness of the patient and the eventual manifestation of the disease is discussed.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0428
    Keywords: Insulin release ; perfused pancreas ; fasting ; phentolamine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Starvation of rats for 24 hrs resulted in decreased insulin release from the isolated rat pancreas. The effect of fasting could not be counteracted by elevation of the glucose level in the equilibration medium from 0.8 to 1.5 mg/ml. The alpha-adrenergic blocking agent phentolamine (10 μg/ml) stimulated glucose induced insulin release to approximately the same extent in fasted as in fed rats. These findings illustrate the importance of endogenous catecholamines in the regulation of insulin secretion from the isolated pancreas. Our experiments suggest that the impairment of insulin secretion on fasting is due neither to the inhibitory effect of catecholamines nor to the lack of substrate in the pancreas at the initiation of the stimulation.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-0428
    Keywords: Somatostatin ; diabetic Chinese hamsters ; islet cells ; A1-cells ; glucagon ; insulin ; hypothalamus ; stomach
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The inhibitory effects of somatostatin on the release of insulin and glucagon, as well as its localization to the A1-cells (D-cells) of the pancreatic islets, suggest a role of this peptide in carbohydrate metabolism. In the present study we have measured the percentage islet volume, the total weight of the A1-cells and the somatostatin concentration in the pancreas of normal and spontaneously diabetic Chinese hamsters. In addition, the concentration of somatostatin in the stomach and hypothalamus as well as the insulin and glucagon content of the pancreas were evaluated. The percentage islet volume in the normal hamsters was 0.66±0.12, which was in marked excess of that in the diabetic group, 0.38±0.04. Similarly, the total weight of the A1-cells in the controls, 0.17±0.02 mg, was significantly larger than that in the diabetic animals, 0.12±0.02 mg. In agreement with these findings there was also a decreased pancreatic concentration of insulin and somatostatin, whereas the glucagon concentration was in the normal range. Also the stomach of the diabetic hamsters showed a decreased concentration of somatostatin. In the hypothalamus the total content of somatostatin appeared similar in the two groups of animals, but when expressed per mg wet weight this value was also decreased in the diabetic hamsters. These observations strongly suggest that, in the diabetic Chinese hamster, apart from the well-known B-cell deficiency there exists also a decreased functional activity of the somatostatin-producing cells.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 4 (1968), S. 1-9 
    ISSN: 1432-0428
    Keywords: Human growth hormone ; Growth hormone ; Insulin ; Diabetes mellitus ; Experimental diabetes ; Acromegaly ; Pathogenesis of diabetes mellitus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé Il a été démontré récemment que l'hormone de croissance humaine (HGH) joue un rôle prééminent dans la régulation normale de la glycémie. De plus, il est bien connu que l'hormone de croissance peut créer un état semblable au diabète chez l'animal. Chez l'homme, l'injection de HGH ou l'hypersécrétion de l'hormone endogène dans l'acromégalie est suivie d'intolérance au glucose seulement dans 25% des cas. — Dans ce travail nous présentons des données qui mettent l'action dite diabétogène de HGH dans un contexte plus nuancé. Nous suggérons que HGH, bien que diminuant l'utilisation du glucose par les tissus périphériques, n'est pas une substance primairement diabétogène, car l'effet insulinotrope de l'hormone cause une hyperinsulinémie compensatrice, qui à son tour normalise la tolérance au glucose. HGH est diabétogène exclusivement chez les sujets prédiabétiques dont le pancréas est incapable de répondre à l'effet insulinotrope de l'hormone. Chez ces sujets, la diabétogénicité de HGH n'étant pas surmontée par une hyperinsulinémie compensatrice, la tolérance au glucose sera anormale. Ainsi, HGH peut être considérée comme unfacteur additif pour la pathogénèse du diabète sucré, la condition essentielle et primaire étant un état préexistant de prédiabète.
    Abstract: Zusammenfassung Wie kürzlich gezeigt wurde, spielt das menschliche Wachstumshormon (HGH) eine wichtige Rolle bei der Kontrolle der Blutzucker-Homöostase. Ferner ist schon lange bekannt, daß die Verabreichung von Wachstumshormon an Tiere zu einem diabetesähnlichen Zustand führen kann. Beim Menschen löst die Gabe der Substanz oder die Überproduktion des endogenen Hormons bei der Akromegalie nur in etwa 25 % der Fälle eine Glucosetoleranzstörung aus. — In dieser Arbeit werden Resultate beschrieben, die ein detaillierteres Bild der sogenannten diabetogenen Wirkung des HGH vermitteln. Wir möchten annehmen, daß das HGH, obwohl es den peripheren Glucoseverbraueh herabsetzt, kein primär diabetogener Faktor ist, da es über eine Insulin-mehrausschüttung zu einem Hyperinsulinismus führt, der eine normale Glucosetoleranz bewirkt. HGH zeigt Scine diabetogene Wirkung nur bei Prädiabetikern, deren Pankreas den stimulierenden Effekt des Hormons auf die Insulinausschüttung nicht beantworten kann. Bei diesen Personen kann eine Störung der Glucosetoleranz dadurch entstehen, daß die diabetogene Wirkung des HGH nicht durch einen kompensatorischen Hyperinsulinismus ausgeglichen wird. HGH kann daher als ein Zusatzfaktor bei der Diabetesentstehung angesehen werden, deren Hauptvorbedingung jedoch eine schon vorher bestehende prädiabetische Stoffwechselsituation darstellt.
    Notes: Summary Human growth hormone (HGH) has recently been shown to play a prominent role in the control of blood glucose homeostasis. Furthermore, it has long been known that administration of growth hormone in animals can induce a diabetes-like state. In human subjects, exogenous administration of HGH or hypersecretion of the endogenous hormone in acromegaly is accompanied by glucose intolerance in only about 25 per cent of the cases. — In this paper, data are presented which give a more diversified picture of the so-called diabetogenic action of HGH. It is suggested that HGH, although decreasing the peripheral utilization of glucose, is not a primary diabetogenic factor, since its insulinogenic action causes a compensatory hyperinsulinism, with normal glucose tolerance as the result. HGH is diabetogenic only in prediabetic subjects whose pancreas is unable to respond to the insulinogenic effect of the hormone. In such subjects, the diabetogenic action of HGH not being counterbalanced by a compensatory hyperinsulinism, glucose intolerance may result. Thus, HGH may be regarded as anadditional factor for the development of diabetes, the major prerequisite being a preëxisting prediabetic state.
    Type of Medium: Electronic Resource
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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: Type 2 (non-insulin dependent) diabetes mellitus ; glucose infusion test ; insulin ; tyrosine hydroxylase ; insulin-like growth factor II ; DNA polymorphisms ; linkage disequilibrium
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The feasibility of disease association studies using polymorphic DNA markers in the tyrosine hydroxylase/insulin/insulin-like growth factor II chromosomal region was indicated by a high degree of linkage disequilibrium found in haplotypes. Haplotypes were resolved in the parents from Scandinavian nuclear families by studying the segregation of eight DNA polymorphisms. Comparison of observed vs expected frequencies of haplotypes, as well as pairwise measures of linkage disequilibrium, indicated a high degree of linkage disequilibrium. Five restriction fragment length polymorphisms linked to the tyrosine hydroxylase/insulin/ insulin growth factor II region of chromosome 11 were investigated in relation to Type 2 (non-insulin-dependent) diabetes mellitus, and to glucose and insulin responses to glucose infusion in healthy subjects. No significant differences in genotype frequencies between Type 2 diabetic (n=53) and healthy subjects (n=106) were found. A significant association (p〈0.001) was initially found between genotypes defined by a PstI polymorphism located 5′ of the tyrosine hydroxylase gene and the early glucose response to a standardized glucose infusion test in healthy subjects. However, a follow-up study of 112 healthy individuals failed to confirm this finding.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-0428
    Keywords: Type 2 (non-insulin-dependent) diabetes mellitus ; insulin receptors ; restriction fragment length polymorphisms ; linkage disequilibrium ; blood glucose
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The significance of insulin receptor gene variants in the aetiology of Type 2 (non-insulin-dependent) diabetes mellitus has been investigated by analysis of restriction fragment length polymorphisms in a genetically homogeneous Swedish population. Seven polymorphisms were analysed, spanning functionally important regions of the insulin receptor locus. Four of these polymorphisms were mapped more accurately within the gene compared to previous studies. The genotype distribution was compared in 76 Type 2 diabetic patients and 84 healthy control subjects. No significant differences were found in the distribution of genotypes between diabetic and control subjects at the p〈 0.01 level. In order to study the possible association between quantitative measures of glucose metabolism and these DNA polymorphisms, the fasting glucose and insulin concentrations were compared in the different genotype groups of control subjects and mildly diabetic patients treated with diet. No differences in fasting glucose or insulin concentrations were found at the p〈 0.005 level of significance. In conclusion, no significant associations were found between insulin receptor gene DNA polymorphisms and glucose intolerance.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1432-0428
    Keywords: Tolbutamide ; insulin secretion in humans ; action of tolbutamide
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé L'effet du tolbutamide intraveineux sur l'insulino-sécrétion a été étudié chez des sujets normaux dans des conditions expérimentales variées. Dans une série d'expériences on laissa baisser la glycémie à la suite du tolbutamide, tandis que dans une autre le sucre sanguin était maintenu dans les limites de la normale grâce à une perfusion de glucose suivant l'injection de tolbutamide. Dans d'autres expériences, le tolbutamide a été administré pendant que les sujets étaient hypoglycé-miques à la suite d'une injection intraveineuse d'insuline. Les résultats obtenus démontrent que le tolbutamide, à condition, de maintenir la glycémie dans les limites de la normale, provoque une insulino-sécrétion aussi bien rapide et de courte durée que prolongée et de type post-initial. L'aspect passager de l'action du tolbutamide chez l'homme normal admis jusqu' à maintenant comme inhérent à la drogue, semble être dû à l'hypoglycémie provoquée par son administration. En effet quand le tolbutamide était administré durant une hypoglycémie plus prononcée, le pouvoir insulinosécréteur de la drogue diminuait encore ou disparaissait totalement. La réponse insulinique à l'hyperglycémie était augmentée par l'administration ultérieure de tolbutamide. Les résultats ci-dessus pourraient être importants pour la compréhension de l'effet thérapeutique du tolbutamide dans le diabète humain.
    Abstract: Zusammenfassung Die Wirkung intravenöser Zufuhr von Tolbutamid wurde bei gesunden Versuchspersonen unter verschiedenen experimentellen Bedingungen untersucht. Den Blutzuckerspiegel ließ man nach der Zufuhr abfallen oder hielt ihn durch gleichzeitige Glucoseinfusion auf normalen Werten. In anderen Versuchen wurde Tolbutamid bei verschiedenen Stufen von Insulinhypoglykämie gegeben. Dabei ergab sich, daß Tolbutamid sowohl eine schnelle und kurzdauernde wie auch eine post-initiale und langdauernde Insulin-freisetzende Wirkung ausübte, vorausgesetzt, daß die Blutzuckerkonzentration auf normaler Höhe gehalten wurde. Die bis jetzt akzeptierte, vorübergehende Tolbutamidwirkung bei Gesunden scheint durch die Hypoglykämie, die der Zufuhr der Droge folgt, verursacht zu sein. Während einer deutlicheren, durch Insulin induzierten Hypoglykämie war die Insulin-freisetzende Wirkung des Tolbutamid fast ausgelöscht. Tolbutamid verstärkte die Insulinfreisetzung auf Glucoseinfusion beträchtlich. Diese Befunde mögen für die Interpretation der therapeutischen Wirkung des Tolbutamid bei Diabetes mellitus von Bedeutung sein.
    Notes: Summary The effect of intravenous tolbutamide on insulin release in normal human subjects was investigated under various experimental conditions. The blood glucose level was either allowed to fall after i.v. tolbutamide or kept within normal limits by a concomitant glucose infusion. In other experiments, tolbutamide was given during different degrees of hypoglycaemia induced by insulin. It was found that tolbutamide provoked a rapid and short-lasting insulin release as well as a post-initial and extended insulin release, provided the blood glucose concentration was kept within normal limits. The hitherto accepted transiency of tolbutamide action in healthy subjects seems to be due to the hypoglycaemia which follows the administration of the drug. During more marked hypoglycaemia induced by exogenous insulin, the insulin releasing capacity of tolbutamide was almost blunted. Tolbutamide markedly enhanced the insulin release following glucose administration. The findings presented might clarify some of the therapeutic effects of the drug in diabetes mellitus.
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 6 (1970), S. 85-89 
    ISSN: 1432-0428
    Keywords: Children ; insulin response ; glucose infusion ; prediabetes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé La réponse insulinique à la perfusion de glucose a été étudiée chez 42 enfants âgés de 7 à 16 ans et ayant un test de tolérance au glucose normal. Chez la plupart des enfants au moins un des parents ou frères et sœurs avait le diabète. Une réponse insulinique réduite et retardée, similaire à celle observée chez 15 à 20% des adultes en bonne santé, a été démontrée chez 7 enfants sur les 42. Ces résultats confirment notre suggestion que ce type de réponse insulinique réduite et retardée est probablement déterminée par des facteurs héréditaires.
    Abstract: Zusammenfassung Die Insulinausschüttung nach Glucoseinfusion wurde bei 42 Kindern, 7–16 Jahre alt, mit normaler intravenösen Glucosetoleranz untersucht. Die Mehrzahl dieser Kinder hatte einen diabeteskranken Eltern-oder Geschwisterteil. Eine verzögerte und verringerte Insulinfreisetzung, ähnlich denen, die bei 15–20% von gesunden Erwachsenen gefunden worden waren, war bei 7 von 42 Kindern zu sehen. Dieser Befund stützt unsere frühere Ansicht, daß die verzögerte und verringerte Insulinausschüttung bei Hyperglykämie wahrscheinlich genetisch bedingt ist.
    Notes: Summary Insulin response to glucose infusion was studied in 42 children with a normal intravenous glucose tolerance, 7–16 years of age. The majority of these children had at least one first degree relative with diabetes mellitus. Low and delayed insulin response similar to the one found in 15–20% of healthy adult subjects also occurred in 15–20 per cent of the children in this material. These findings support our previous suggestion that the low and delayed insulin response to glucose is probably genetically determined.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 14 (1978), S. 1-13 
    ISSN: 1432-0428
    Keywords: Somatostatin ; hypothalamus ; hypophysis ; growth hormone ; insulin secretion ; neurotransmitters
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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