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  • 1
    ISSN: 1432-0428
    Keywords: Chinese hamster ; Cricetulus griseus ; spontaneous diabetes ; pancreatic islets ; islets of Langerhans ; beta cell mitosis ; beta cell hyperplasia ; autoradiography ; insulin ; diabetes remission ; adrenal glucocorticoid
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Light microscopic and autoradiographic studies were performed in normal genetic nondiabetic and diabetic Chinese hamsters after the administration of thymidine-3H and correlated with levels of blood glucose (BG) and plasma insulin (IRI). Pancreatic islets of normal hamsters contained well granulated beta cells; rare islet cells incorporated thymidine-3H and the IRI/BG ratio (I/G) was =1.91. Recent onset diabetics revealed hyperglycemia and hyperinsulinemia (I/G = 1.97), beta cell degranulation and increased islet cell labelling. With progression of diabetes, I/G ratios decreased (Non-ketotic animals: 1.08, Ketotic hamsters: 0.17), beta cell numbers declined and islet labelling was infrequent. Hamsters with spontaneous remission from diabetes showed normoglycemia, hyperinsulinemia (I/G = 2.84) and beta cell hyperplasia. Glucocorticoid administration to normal hamsters induced marked BG elevations, beta cell hyperplasia and increased thymidine-3H incorporation. The absence of increased beta cell labelling among most diabetics treated with glucocorticoids may be a manifestation of a genetically defined defect of beta cell replication that is in part responsible for the declining beta cell mass and insulin synthetic capacity of the diabetic Chinese hamsters.
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  • 2
    ISSN: 1432-0428
    Keywords: Chinese hamster ; prediabetes ; diabetes diet-limitation ; diabetes prevention ; diabetes ameliorati on, and increased longevity.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Prediabetic Chinese hamsters born of two ketonuric diabetic parents were hyperphagic from birth. Carcass lipids and total solids were increased but plasma and pancreatic insulin were not, suggesting that hyperphagia was not due to hyperinsulinism. Hyperphagia was controlled by diet limitation of prediabetic pups. Diet limitation for the weaning period only did not alter development of diabetes, but diet limitation for the first 150 days significantly reduced onset and severity. These 150 day diet-limited prediabetics were switched to nonrestricted feeding and subsequently developed mild diabetes. Prediabetic siblings, fedad libitum, developed glucosuria and ketonuria, and died prematurely compared with diet-limited siblings. Prediabetics limited to a normal food intake for 30 months have remained essentially clinically normal. The data strongly suggest that appetite control mechanisms are abnormal prior to clinical signs of diabetes in the prediabetic Chinese hamster and that control of hyperphagia will retard anameliorate the course of diabetes.
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  • 3
    ISSN: 1432-0428
    Keywords: Chinese hamster ; Cricetulus griseus ; endocrine pancreas ; islet of Langerhans ; A-cells ; B-cells ; D-cells ; spontaneous diabetes ; nuclear pores ; plasma membrane ; membrane-associated particles ; glycogen ; ultrastructure ; electron microscopy ; freeze-etching
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The nuclear and plasma membranes of islet cells from non-glycosuric and diabetic Chinese hamsters were examined by freeze-etching. The B-cells of diabetic animals presented a slight increase in the number of nuclear pores and marked alterations in the number, size and distribution of membrane-associated particles in the plasma membrane. In A-cells, identified by the presence of characteristic bundles of coarse filaments in the perinuclear region, a definite increase in the number of nuclear pores was found in the most severely diabetic animals. These preliminary findings point to alterations in the membrane systems as possible determinants for the abnormalities of islet function in diabetes mellitus.
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  • 4
    ISSN: 1432-0428
    Keywords: Toronto-KK mouse ; diabetes in animals ; gluconeogenesis ; insulin synthesis and secretion ; islets of Langerhans ; obesity ; gluconeogenic enzymes ; glycolytic enzymes ; B-cell degranulation ; islet RNA synthesis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The activities of six hepatic enzymes were assayed in six-month old Toronto-KK and C57BL/6J mice. Activities of hepatic gluconeogenic enzymes (phosphoenolpyruvate carboxykinase, glucose-6-phosphatase, fructose-1,6-diphosphatase) were significantly elevated in Toronto-KK mice while activities of glycolytic enzymes (glucokinase, hexokinase, pyruvate kinase) remained normal. Isolated islets of Langerhans obtained from Toronto-KK mice demonstrated significantly elevated levels of insulin secretion and of insulin and RNA biosynthesis in response to glucose stimulation. Islets of Toronto-KK mice were markedly hyperplastic and showed pronounced B-cell degranulation after stimulation with glucose. The data suggest that hyperglycemia appears to result, in part, from excessive gluconeogenesis. Hyperinsulinemia appears to result from excessive insulin synthesis and release from the pancreatic islets in response to glucose stimulation.
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  • 5
    ISSN: 1432-0428
    Keywords: Chinese hamster ; spontaneous diabetes ; glucosuria ; ketonuria ; glycogen ; glycogen accumulation ; retina ; Müller cell ; kidney ; distal tubule ; pancreatic islet ; a cell ; Β cell ; D cell ; electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Intracellular glycogen deposits were consistently found in the retina, kidney and pancreatic islets of diabetic-ketonuric Chinese hamsters. Accumulation of glycogen in the outer nuclear layer of the retina was mostly associated with severity of the disease, but was not related to age or sex. The type of retinal cell involved in the accumulation of glycogen was not clearly established. However, the position of the affected cell, side by side with retinal neurons, suggests that the glycogen deposits were within Müller cells. These giant glias normally synthesize and store glycogen. All ketonuric Chinese hamsters examined showed some accumulation of glycogen in distal tubules of the kidney. This abnormal glycogen was not found in glucosuric non-ketonuric or in nondiabetic Chinese hamsters. Variable amounts of glycogen were found inΒ cells of pancreatic islets of diabetic hamsters, as reported by others. However, accumulation of glycogen was also found inα and D islet cells from 2 middle aged Chinese hamsters with long term glucosuria and recent ketonuria. Abnormal glucose and glycogen metabolism seem to play an important role in the pathogenesis of diabetes in the Chinese hamster.
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  • 6
    ISSN: 1432-0428
    Keywords: Diabetes ; hamster ; neuropathy ; teased-fiber ; ultrastructure ; demyelination ; axonal degeneration ; onion-bulb ; nerve fiber ; peripheral nerve
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Distal tibial nerves of 14 chronically diabetic and 6 control Chinese hamsters were examined using ultrastructural and teased whole-mount methods. Glucosuria was present for varying intervals up to 976 days, while 10 hamsters manifested ketonuria for intervals up to 551 days. Myelin internodal ensheathment patterns were analyzed from whole-mount preparations. A normal proportional relationship existed between myelin internodal length and fiber size in the peripheral nerves from control animals. Patterns of segmental demyelination were seen in the internode length/fiber size relationships of experimental animals. These changes were manifested by increased disparity of internode lengths along individual medullated fibers as well as by a generalized decrease of internode lengths, especially along large fibers. In addition, occasional fibers were seen undergoing acute axonal (Wallerian) degeneration in teased fiber preparations of diabetic animals. Variations in severity of structural alterations correlated with the length of diabetic state and were markedly increased in some animals with ketonuria. Examinations of some proximal sciatic nerves gave indications of a marked proximo-distal gradient in the manisfestations of the structural alterations in peripheral nerve. Electron microscopic evidence of demyelinative and remyelinative phenomena could be seen in diabetic hamsters. Both light and electron microscopic changes in diabetic animals were similar to those reported in diabetic neuropathy.
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 10 (1974), S. 601-606 
    ISSN: 1432-0428
    Keywords: Chinese hamster ; diabetes mellitus ; cholesterol ; aorta ; endothelium ; intima ; smooth muscle cell ; elastic tissue ; collagen ; calcium
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Light and electron microscopic observations of the thoracic aortas of hypercholesterolemic, diabetic Chinese hamsters compared with normocholesterolemic, nondiabetic matched controls revealed significant ultrastructural changes in the diabetic animals. Endothelial cells frequently contained osmiophilic lipid droplets. Smooth muscle cells were identified in the intima and the adjacent extracellular space of the intima contained abundant electron dense, amorphous material suggestive of elastin or fragmented internal elastic lamella. Calcium deposits were present in the media and surrounded by collagen fibers and pale, amorphous material consistent with ground substance. These changes were not observed in nondiabetic Chinese hamsters and may represent significant alterations that predispose the aorta to more extensive pathologic changes.
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 6 (1970), S. 317-323 
    ISSN: 1432-0428
    Keywords: Spontaneous diabetes ; KK mice ; insulin ; resistance to insulin ; diet and sensitivity to insulin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé La tolérance au glucose est anormale chez beaucoup de souris mâles KK bien que le taux du sucre sanguin à jeun soit généralement normal. La glucosurie des souris KK est intermittente et le sucre sanguin des souris non soumises au jeûne est élevé chez certaines d'entre elles. Le taux d'insuline plasmatique des souris KK non soumises au jeûne est 10 à 100 fois plus élevé que celui des souris non-diabétiques et l'insuline pancréatique est 50% plus élevée que celle des souris témoins. Le diaphragme et le tissu adipeux des souris KK sont insensibles à l'insulinein vitro, la captation de base du glucose par le muscle diaphragmatique des souris KK est normale tandis que l'oxydation de base du glucose par le tissu adipeux est significativement plus basse dans le tissu obtenu des souris KK. Un régime calorique limité abaisse le taux d'insuline plasmatique et le poids corporel; de même qu'il rétablit une sensibilité normale du tissu adipeux à l'insuline. Il est postulé que le diabète des souris KK est dû à une diminution de la sensibilité du tissu adipeux et du muscle à l'insuline endogène et à une augmentation de la prise alimentaire qui a pour résultat une augmentation de la demande en insuline. Le pancréas répond à cette demande par une augmentation de la sécrétion d'insuline et par des taux insuliniques élevés et, pour autant que ces conditions persistent, une hyperthrophie des îlots de Langerhans en résulte. La reproduction consanguine des souris KK a produit des animaux présentant seulement quelques anomalies. Les animaux de la 4e jusqu'à la 7e génération dérivés de souche consanguine KK×C57 BL/6J présentent un nombre relativement grand d'animaux anormaux.
    Abstract: Zusammenfassung Trotz gegenüber der Norm um 50% erhöhtem Pankreasinsulingehalt und 10–100-fach erhöhter Plasmainsulinkonzentration zeigten die KK-Mäuse der untersuchten Population intermittierende Glykosurie. Bei zahlreichen Tieren war die Glucosetoleranz trotz normaler Nüchternblutzuckerwerte vermindert.In vitro sprachen weder das Zwerchfell noch das epididymale Fettgewebe der KK-Mäuse auf Insulin an. In Abwesenheit von Insulin war die Glucoseaufnahme der Zwerchfellmuskeln normal, wogegen die Glucoseoxidation im Fettgewebe von KK-Mäusen gegenüber der Norm deutlich erniedrigt war. Kalorienrestriktion hatte ein Absinken der Plasmainsulin-Konzentrationen und des Körpergewichts zur Folge und stellte die Insulinempfindlichkeit des Fettgewebes wieder her. Die Autoren nehmen an, daß der Diabetes der KK-Maus auf eine Verminderung der peripheren Insulinempfindlichkeit sowie übermäßige Calorienaufnahme zurückzuführen sei. Die Hyperinsulinemie und die Hypertrophie der Langerhans'schen Inseln des Pankreas werden als Konsequenzen des erhöhten Insulinbedarfs aufgefaßt. Kontinuierliche Inzucht von KK-Mäusen vermindert die Häufigkeit von Stoffwechselanomalien, dagegen wurde sie durch Kreuzung von KK-Mäusen mit einem Stamm von normalen Tieren ab der 4. Generation deutlich gesteigert.
    Notes: Summary Glucose tolerance was abnormal in many male KK mice studied although fasting blood sugars were generally normal. Glucosuria of KK mice was intermittent and nonfasting blood sugar was elevated in some. Plasma insulin of nonfasted KK mice was 10–100 times that of nondiabetic mice and pancreatic insulin was 50% higher than that of control mice. The diaphragm and fat pads of KK mice were insensitive to insulinin vitro. The baseline glucose uptake by diaphragm muscles of KK mice was normal, whereas baseline glucose oxidation by adipose tissue was significantly lower in tissue from KK mice. Limited diet lowers plasma insulin and body weight and restores the adipose tissue sensitivity to insulin. It is postulated that diabetes in the KK mouse is due to decreased sensitivity of fat and muscle to endogenous insulin and to increased food intake which results in an increased demand for insulin. The pancreas responds to this demand by increased insulin secretion and elevated plasma insulin, and as this condition continues, islet hypertrophy results. Continued inbreeding of KK mice produced animals with fewer abnormalities. Fourth to seventh generation animals derived from inbreeding offspring from KK×C57 BL/6J mice exhibited relatively large numbers of abnormal animals.
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  • 9
    ISSN: 1432-0428
    Keywords: Diabetes in animals ; Chinese hamster ; cricetulus griseus ; ketotic diabetes ; islet of Langerhans ; β-cells ; B-cells ; B-cell volume ; conjugal diabetes ; offspring of diabetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé Des hamsters chinois provenant de la colonie des Laboratoires Upjohn ont été étudiés à différents âges allant de 15 jours à 19 mois. On trouve une glycosurie et une hyperglycémie chez les animaux diabétiques de 3 à 6 mois et chez ceux de 10 à 19 mois. On observe également une cétonurie et une cétonémie, mais les taux de glycérol sanguin et les taux d'insuline plasmatique à jeun sont bas par comparaison à ceux détectés chez des témoins d'âge comparable. Le volume des îlots, des cellulesβ et des granulesβ, mesuré par des méthodes quantitatives élaborées dans notre laboratoire, est diminué. Le volume des cellules non-granulées augmente progressivement avec la durée du diabète. On observe une infiltration de glycogène dans les cellules B des animaux diabétiques. Bien que la progéniture, âgée de 15 jours, de deux animaux sévèrement diabétiques (avec cétose) ait des taux normaux de glycémie et une glycosurie, leur insulinémie est plus élevée que celle mesurée chez les témoins. Le volume de leurs îlots est un peu plus grand que celui des contrôles, mais, en microscopie optique et électronique, les cellulesβ sont dégranulées et montrent une infiltration de glycogène. Ces résultats confirment l'hypothèse que le défaut primaire est au niveau de la biosynthèse de l'insuline.
    Abstract: Zusammenfassung Mit von den Autoren entwickelten morphometrischen Methoden wurde das B-Zell-Volumen im Pankreas chinesischer Hamster der Upjohn Kolonie bestimmt. Das Alter der untersuchten Tiere schwankte zwischen 15 Tagen und 19 Monaten. Die diabetischen Tiere waren entweder 3 – 6 oder 10–19 Monate alt. Sie waren hyperglykämisch und glykosurisch, teilweise bestand Ketonurie. Die Plasmainsulin- und Glyzerin-Konzentrationen im Gesamtblut waren niedriger als diejenigen gleichaltriger Normaltieren erniedrigt. Bei diabetisehen Tieren waren B-Zell- undβ-Granula-Volumen vermindert. Mit zunehmender Dauer des Diabetes nahm der Anteil der nicht granulierten B-Zellen zu. Die B-Zellen diabetischer Tiere zeigten Glykogeninfiltration. 15 Tage alte Nachkommen zweier ketotisch-diabetischer Eltern waren normoglykämisch, hatten aber im Vergleich zu gleichaltrigen Kontrolltieren erhöhte Plasmainsulin-Konzentrationen. Das Inselzellvolumen war gegenüber der Norm erhöht, aber die B-Zellen waren degranuliert und zeigten Glykogeninfiltration. Diese Resultate stimmen mit der Hypothese überein, daß der primäre Defekt, der beim chinesischen Hamster die Entwicklung eines diabetischen Syndroms zur Folge hat, die Biosynthese des Insulins betrifft.
    Notes: Summary Chinese hamsters bred at the Upjohn Laboratory were studied at varying ages from 15 days to 19 months. Diabetic animals three to six months and those 10 to 19 months of age were glycosuric and hyper glycemic; there was ketonuria and ketonemia but blood glycerol and fasting plasma insulin levels were low when these values were compared with normal control animals of comparable ages. Using quantitative technics developed in our laboratory, the volumes of islets, beta cells and beta granules were diminished. The increase in volume of nongranular cells is progressive with duration of diabetes. Glycogen infiltration was observed in beta cells of these diabetic animals. — Although offspring (fifteen-day-old weanlings) of the mating of two severely diabetic (ketotic) animals were normoglycemic and glycosurie, their plasma insulin levels were higher than those of their controls. The islet volume was somewhat higher than that of the controls but the beta cells were degranulated both by light and electron microscopy; the beta cells exhibited glycogen infiltration. These results are consistent with the thesis that the primary defect is in insulin biosynthesis.
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  • 10
    ISSN: 1432-0428
    Keywords: Spontaneous diabetes ; chinese hamster ; cricetulus griseus ; epidemiology ; genetics of diabetes ; conjugal diabetes in animals ; diabetes in animals ; inheritance of diabetes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé Le glucose et les corps cétoniques urinaires de 253 hamsters nés entre janvier et septembre 1968 ont été mesurés toutes les deux semaines à partir de l'âge de 15 jours jusqu'en septembre 1969. Ces animaux proviennent de 67 nichées produites par 28 femelles mariées à 19 mâles de 7 lignées consanguines. — Tous les 46 hamsters provenant de parents diabétiques avec cétose sévère sont devenus diabétiques (continuellement 4+ au Tes-Tape). 25 parmi ces 46 animaux ont développé une cétonurie (continuellement 4 + au Ketostix). — Alors que 100% des animaux de parents diabétiques avec cétose sont devenus diabétiques en 8 mois, on trouve une incidence de diabète de 59% chez des animaux provenant de croisements entre animaux diabétiques cétosiques et non-cétosiques; cette incidence est de 41% chez les animaux provenant de parents cétosiques diabétiques mais avec des animaux ayant des traces de glycosurie; elle est de 24% chez ceux provenant de croisements d'animaux diabétiques cétosiques avec des non-diabétiques. — Le diabète apparaît plus tôt dans la progéniture d'animaux diabétiques avec cétose que chez celle issue d'animaux avec diabète léger. A l'âge de 3 semaines, parmi les petits de parents ayant un diabète cétosique, 26% montraient des traces de glycosurie, 26% étaient diabétiques et 2% étaient cétosiques. A l'âge de 2 mois, 85% sont devenus diabétiques. A l'âge de 3 semaines, les petits issus de mariages entre parents avec diabète cétosique et noncétosique ont présenté des traces de glycosurie dans 16% des cas et un diabète dans 2% des cas. Seulement 36% étaient diabétiques à l'âge de 2 mois. — Les animaux de hamsters chinois avec diabète cétosique sévère se prêtent de façon idéale à des recherches sur le prédiabète, parce que l'apparition de la maladie est prévisible et que, de plus, ces animaux deviennent rapidement diabétiques confirmant ainsi leur état prédiabétique antérieur. Chez la progéniture de parents ayant un diabète moins sévère, son apparition est imprévisible du fait que 59% seulement ont dévélopé un diabète et que la fréquence de la maladie varie de nichée à nichée issues de mêmes parents. Par ailleurs, on sait que des parents non-diabétiques ont eu des petits diabétiques. Ces données suggèrent que la transmission du diabète chez le hamster chinois est complexe puisqu'elle ne peut pas être expliquée par la présence d'un seul gène récessif.
    Abstract: Zusammenfassung 253 zwischen Januar und September geborene chinesische Hamster wurden ab dem 15. Lebenstag und bis September 1969 in zweiwöchigen Abständen auf das Vorliegen von Zucker und Ketonkörper im Urin untersucht. Es handelte sich um Tiere aus 67 Würfen von 28 Weibchen und 19 Männchen aus 7 verschiedenen Inzuchtlinien. Alle 46 Nachkommen schwer ketotisch diabetischer Eltern entwickelten einen Diabetes, der bei 25 Tieren auch von Ketonurie begleitet war. Innerhalb der ersten 8 Lebensmonate wurde ein Diabetes festgestellt bei 100% der Nachkommen ketotisch-diabetischer Eltern, bei 59% der Nachkommen eines ketotisch-diabetischen und eines nicht ketotisch-diabetischen Elternteils, bei 41% der Nachkommen eines ketotischen und eines nur spurenweise glykosurischen Tieres und bei 24% der Nachkommen eines ketotischen und eines nicht diabetischen Elternteils. Bei den Nachkommen ketotisch-diabetischer Eltern trat der Diabetes früher auf als bei denen von Eltern mit milderen Formen des Syndroms. 3 Wochen nach der Geburt zeigten 26% der Nachkommen ketotisch-diabetischer Eltern spuren-weise Glykosurie, 26% waren diabetisch und 2% ketonurisch. Zwei Monate nach der Geburt waren 85% der Tiere diabetisch. Bei 3 Wochen alten Nachkommen eines ketotisch diabetischen und eines nicht ketotisch-diabetischen Elternteils waren die entsprechenden Werte 16% für spurenweise Glykosurie, 2% für Diabetes, und im Alter von 2 Monaten waren nur 36% der Tiere diabetisch. — Auf Grund dieser Ergebnisse wird geschlossen, daß sich Nachkommen ketotisch-diabetischer chinesischer Hamster geradezu ideal für die Untersuchung des prädiabetischen Syndroms eignen, da sie alle diabetisch werden und damit der endgültige Beweis für das Bestehen eines prädiabetischen Zustandes in kurzer Zeit erbracht werden kann. Bei Nachkommen weniger schwer diabetischer Eltern kann eine sichere Voraussage nicht gemacht werden, da nur 95% der Tiere einen Diabetes entwickeln und auch dieser prozentsatz von Wurf zu Wurf der gleichen Eltern stark schwanken kann. Da außerdem auch Nachkommen nichtdiabetischer Eltern Diabetes entwickeln können, scheint es daß die Heredität des diabetischen Syndroms des chinesischen Hamsters komplexer Natur ist und nicht auf Grund des Einflusses eines einzelnen rezessiven Gens erklärt werden kann.
    Notes: Summary Two hundred and fifty-three hamsters born between January and September 1968 have been continuously tested biweekly for urine glucose and ketones from 15 days of age through September 1969. They comprise 67 litters out of 28 females sired by 19 males from 7 inbred lines. — All 46 hamsters from two severe ketotic diabetic parents have become diabetic (consistent 4+ Tes-Tape rating). Twenty-five of the 46 have developed ketonuria (consistent 4 + Ketostix rating). — While 100% of the litters from ketotic diabetics became diabetic within 8 months, the incidence of diabetes from ketotic diabetic to nonketotic diabetic matings was 59%; ketotic diabetic to trace glucosuric 41%; and ketotic diabetic to nondiabetic 24%. — Diabetes developed earlier in progeny from ketotic diabetics than in those from milder diabetics. At 3 weeks, pups from ketotic diabetics were 26% trace glucosuric, 26% diabetic, 2% ketotic and by 2 months 85% diabetic. At 3 weeks, descendents from ketotic diabetics mated to nonketotic diabetics were 16% trace glucosuric, 2% diabetic and by 2 months only 36% diabetic. — Animals from severely ketotic diabetic Chinese hamsters are ideally suited for prediabetes research since they are predictable and rapidly become diabetic as proof of their earlier prediabetic state. Progeny from less severe diabetic parents are not predictable since only 59% developed diabetes and the incidence varied from litter to litter from the same parents. Further, nondiabetic parents have produced diabetic offspring. The data suggest that the inheritance of diabetes in chinese hamsters is complex since it cannot be explained by a single recessive gene.
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