Summary
Diabetes in Chinese hamster was initially detected by qualitative tests for urine glucose. The disease was characterized by quantitating urine glucose, glucose tolerance tests and measurement of fasting and nonfasting blood sugar, blood ketones, plasma free fatty acids (FFA), plasma insulin, pancreatic insulin and fasting levels of liver glycogen. In addition, basal levels of glucose utilization by diaphragms and epididymal adipose tissue and the response of these tissues to insulin was measured. Those animals requiring insulin received their last injection 24 hours prior to study. Glucosuria varied from 51 to 1600 mg/24 hours. Diabetics had significantly decreased tolerance to a 250 mg/kg glucose load. The response varied considerably in diabetics but was uniform in the nondiabetics. Diabetics had mean fasting liver glycogen levels of 3.1±1.0 compared with 0.4± 0.7 percent of fresh liver weight for nondiabetics. Severely ketotic, diabetic Chinese hamsters had significantly elevated FFA and ketone levels and significantly lower plasma and pancreatic insulin levels but mild diabetics did not differ from controls with respect to these parameters. All Chinese hamsters had high plasma FFA levels (nondiabetics 1800μE/l, severe diabetics 2800μE/l. Fasting and nonfasting FFA levels did not differ in mild diabetic and nondiabetic animals. Muscle and adipose tissues from diabetic hamsters had basal rates similar to nondiabetics and had similar responses to insulin. Hamsters maintained on insulin had greatly elevated immunoreactive insulin levels in their plasma, which persisted for 26 days. — The data suggest that severely diabetic hamsters may have a decreased ability of the pancreas to secrete insulin in response to a glucose stimulus. The observations that plasma insulin levels are normal in mild diabetics but that these animals have glucosuria, hyperglycemia and abnormal glucose tolerance suggest that mild diabetes in the Chinese hamster may involve interference with insulin action and/or increased hepatic glucose output.
Résumé
Nous avons dépisté le diabète chez le hamster chinois par des dosages qualitatifs de la glucosurie. Nous avons ensuite caractérisé chaque cas par la mesure quantitative du glucose urinaire, par des surcharges au glucose et par le dosage de la glycémie à jeun et non à jeun, des corps cétoniques, des acides gras libres (AGL) plasmatiques, de l'insuline plasmatique et pancréatique, et des taux hépatiques de glycogène. En outre, nous avons mesuré l'utilisation du glucose par le diaphragme et le tissu adipeux épididymaire, avec et sans stimulation par l'insuline. Les animaux nécessitant l'administration d'insuline ont reçu leur dernière injection au moins 24 heures avant chaque étude. Les taux de glucose dans l'urine ont varié entre 51 et 1600 mg par 24 heures. Le test de surcharge au glucose s'est révélé nettement anormal chez les animaux diabétiques, la surcharge étant de 250 mg de glucose par kg de poids. Chez les diabétiques, la glycémie après surcharge est fortement variable, contrairement à l'uniformité de la réponse observée chez les non-diabétiques. Le glycogène hépatique à jeun est de 3, 1±1,0% pour les diabétiques, et de 0,4±0,7% de poids frais d'organes pour les non-diabétiques. Les taux plasmatiques des AGL et des corps cétoniques sont manifestement élevés chez les hamsters chinois diabétiques et cétosiques alors que le contenu en insuline du plasma et du pancréas est abaissé de façon marquée. Ceci n'a pas été observé chez les diabétiques moins sévères qui se rapprochent des non-diabétiques. Les AGL plasmatiques sont élevés chez tous les hamsters chinois (moyenne pour les non-diabétiques 1800μE/l, pour les diabétiques sévères 2800μE/l) Les taux d'AGL sont les mêmes à jeun et non à jeun chez les animaux non-diabétiques ou souffrant d'un diabète léger. L'utilisation du glucose par le muscle et le tissu adipeux du hamster diabétique ne diffère pas significativement de celle des tissus non-diabétiques et leur stimulation par l'insuline est semblable. L'insuline immunoréactive des hamsters traités à l'insuline reste élevée dans le plasma pendant plus de 26 jours après la dernière injection. — Ces observations semblent indiquer que le pancréas des hamsters chinois diabétiques sécrète plus difficilement de l'insuline en réponse à une stimulation par le glucose. Les taux normaux d'insuline plasmatique chez les hamsters avec un diabète léger, mais présentant pourtant une nette glucosurie, une hyperglycémie et une réponse anormale à la surcharge en glucose, suggèrent l'existence d'une interférence avec l'action normale de l'insuline et peut-être une augmentation de la production de glucose par le foie.
Zusammenfassung
Beim chinesischen Hamster wurde der Diabetes durch qualitative Urinuntersuchungen auf Glucose aufgespürt. Es wurde dann jeder Fall näher charakterisiert durch quantitative Uringlucosebestimmungen, Glucosebelastungsproben und Messungen von Nüchtern- und Nichtnüchternwerten für Blutzucker, Blutketonkörper, freie Fettsäuren (FFS) und Insulin im Plasma, von Insulin im Pankreas, und von Nüchternwerten für Leberglykogen. Außerdem wurde der Glucoseverbrauch des Zwerchfells und des epididymalen Fettgewebes sowie mit, als auch ohne Insulin gemessen. Diejenigen Tiere, die Insulin erforderten, erhielten ihre letzte Injektion 24 Stunden vor dem Versuch. Glucosurie schwankte zwischen 51 und 1600 mg/24 Std. Bei einer Belastung von 250 mg/kg wiesen die diabetischen Tiere eine wesentlich verminderte Glucosetoleranz auf. Sie sprachen sehr unterschiedlich auf die Glucosebelastung an, während die nichtdiabetischen Tiere in ihrer Reaktion einheitlich waren. — Im Vergleich zu den nichtdiabetischen Hamstern, wo die Mittelwerte für Nüchternleberglykogen bei 0.4±0.7 Prozent des Frischlebergewichtes lagen, hatten die diabetischen Tiere einen Glykogengehalt der Leber von 3.1±1.0 Prozent. — Chinesische Hamster mit schwerem Diabetes haben deutlich erhöhte FFS-Werte und Ketonkörper, sowie einen wesentlich niedrigeren Plasma- und Pankreasinsulinspiegel. Bei Tieren mit leichter Diabetes hingegen sind diese Untersuchungen, im Vergleich zu den Kontrolltieren, unverändert. Alle chinesischen Hamster haben hohe Plasma-FFS-Werte (nichtdiabetische 1800μE/L, schwer diabetische 2800μE/L). Nüchtern- und Nichtnüchternwerte für FSS sind beim leicht diabetischen oder gesunden Tier etwa gleich hoch. Der Glucoseabbau durch Muskel- und Fettgewebe des diabetischen und nichtdiabetischen Hamsters unterscheidet sich nicht sehr, und beide Gruppen sprechen ungefähr gleich stark auf Insulinstimulierung an. Das im Plasma der insulinbehandelten Tiere vorkommende immunreaktive Insulin ist noch 26 Tage nach der letzten Injektion nachweisbar. — Diese Ergebnisse lassen vermuten, daß der Pankreas des diabetischen Hamsters nur schwerlich in der Lage ist, nach einer Glucosestimulierung Insulin auszuschütten. Die Beobachtung, daß der Plasma-Insulinspiegel im leichten Diabetes normal ist, diese Tiere jedoch Glucosurie, Hyperglykämie und abnormale Glucosetoleranz aufweisen, führt zu der Annahme, daß ein leichter Diabetes beim chinesischen Hamster eine Beeinträchtigung der Insulinwirkung mit sich bringen, und Ursache einer vermehrten Glucoseproduktion durch die Leber sein kann.
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Gerritsen, G.C., Dulin, W.E. Characterization of diabetes in the Chinese hamster. Diabetologia 3, 74–84 (1967). https://doi.org/10.1007/BF01222182
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DOI: https://doi.org/10.1007/BF01222182