Summary
The mutation, diabetes (db), that occurred in the C57BL/Ks strain of mice is a unit autosomal recessive gene with full penetrance, and causes metabolic disturbances in homozygous mice resembling diabetes mellitus in man. Abnormal deposition of fat at 3 to 4 weeks of age is followed by hyperglycemia, polyuria and glycosuria. The diabetic condition appears to develop in two stages. In the early stage, there are marked increases in the levels of plasma insulin, the rates of lipogenesis, gluconeogenesis, and glucose oxidation, and there is a reduction ofβ-cell granules in the islet of Langerhans with other changes suggestive of a compensating adaptation to increased insulin demand. On the other hand, the late stage is characterized by a near normal level of circulating insulin, a marked decrease in glucose utilization but with a continued high rate of gluconeogenesis. These findings suggest a defect in the peripheral utilization of insulin rather than in the synthesis and release of the hormone from the pancreas.
Résumé
La mutation, diabète (db), a été observée dans la souche de souris C57BL/Ks. C'est un gène autosomal récessif avec pénétrance complète, et qui mène chez les homozygotes à un trouble métabolique ressemblant au diabète sucré chez l'homme. Une accumulation excessive de graisses se produit à l'âge de 3–4 semaines et est bientôt suivie par l'apparition d'hyperglycémie, de polyurie et de glucosurie. L'évolution clinique suit ensuite deux étapes. Durant la première, les taux d'insuline plasmatique sont élevés et la lipogénèse, la gluconéogénèse, ainsi que l'oxydation du glucose sont accélérées; il y a diminution de la granulation des cellulesβ et d'autres altérations suggérant l'existence d'une compensation d'un état nécessitant une utilisation insulinique accrue. La deuxième étape, par contre, est caractérisée par des taux normaux d'insuline plasmatique, avec diminution marquée de l'utilisation du glucose malgré la persistance d'une gluconéogénèse nettement exagérée. Ces observations nous semblent indiquer l'existence d'une utilisation défectueuse de l'insuline à la périphérie, plutôt qu'une anomalie primaire de la synthèse ou de la libération de l'hormone au niveau du pancréas.
Zusammenfassung
Die Mutation Diabetes (db), die in dem Mäusestamm C57BL/Ks auftritt, ist ein autosomales rezessives Gen mit voller Penetranz und verursacht bei homzygoten Mäusen eine dem im Menschen auftretenden Diabetes mellitus ähnliche Stoffwechselstörung: übermäßige Ablagerung von Fett im Alter von 3–4 Wochen, mit anschließender Hyperglykämie, Polyurie und Glucosurie. Der klinische Verlauf erfolgt dann in zwei Phasen. In der ersten Phase ist ein wesentlicher Anstieg der Plasmainsulinwerte im Vordergrund, mit Beschleunigung von Lipogenese, Gluconeogenese und Glucoseoxydation. Das Abnehmen der Granula in denβ-Zellen der Langerhansschen Inseln und andere Veränderungen deuten auf eine Anpassung an einen steigenden Insulinbedarf. In der zweiten Phase, dagegen, sind die Insulinspiegel eher normal, und der Glucoseverbrauch nimmt ab, bei Weiterbestehen der beschleunigten Gluconeogenese. Diese Ergebnisse deuten eher auf eine mangelhafte periphere Insulinwirkung als auf eine ungenügende Synthese der Ausschüttung des Hormones durch das Pankreas.
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Supported in part by United States Public Health services grant # AM 06871 from the National Institute of Arthritis and Metabolic Diseases and grant # HD 00468 from the National Institute of Human Development.
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Coleman, D.L., Hummel, K.P. Studies with the mutation, diabetes, in the mouse. Diabetologia 3, 238–248 (1967). https://doi.org/10.1007/BF01222201
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DOI: https://doi.org/10.1007/BF01222201