Studies with the mutation, diabetes, in the mouse

Coleman, D L; Hummel, Katharine P.

doi:10.1007/bf01222201

Cited by 322 publications

(236 citation statements)

References 24 publications

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“…Thus, in the young db mouse, when the rate of glucose oxide. tion is accelerated [3], the level of glyeolytie and penrose phosphate shunt enzymes is also elevated. Conversely, in old db, retardation of glucose oxidation [3] is accompanied by depressed activity of pyruvate kinase and 6-phosphogluconate dehydrogenase.…”

Section: Discussionmentioning

confidence: 99%

“…tion is accelerated [3], the level of glyeolytie and penrose phosphate shunt enzymes is also elevated. Conversely, in old db, retardation of glucose oxidation [3] is accompanied by depressed activity of pyruvate kinase and 6-phosphogluconate dehydrogenase. It appears that insulin may play a crucial role in regulating these changes becaues of the following observations: these enzymes are 1. undisturbed in young db with normal plasma and panereatic insulin level, 2. elevated in mice with high plasma insulin, and 3. depressed in mice with normal plasma insulin and depleted pancreatic insulin [4].…”

Section: Discussionmentioning

confidence: 99%

“…Des 6tudes in vivo ont indiqu6 que l'hyperglyc6mie r6sulte, ell partie du moins, d'une glucon6o-g@n~se aec@l@r@e. L'apparition du diab&te chez la souris est discut6e ~ la lumi@re de ees r6sultats. The mutant strain db/db of C 57 BL/Ks mouse develops diabetie syndromes resembling those found in man [3]. Its diabetic symptoms appear to manifest in two stages.…”

Section: Anomalies D'activit~s Enzymatiques H~patlques Pendant Le D~vunclassified

“…Its diabetic symptoms appear to manifest in two stages. The early period is characterized by excessive plasma insulin, reduction in fl-eell granules, increase in glucose oxidation and elevated level of gluconeogenle and lipogenie enzymes, whereas in the later stage, there is a normal plasma insulin level, retarded glucose oxidation, and high gluconeogenie enzyme activity [3]. The symptomatic changes during the development of diabetes signify certain causative biochemical derangements in the db mouse.…”

Section: Anomalies D'activit~s Enzymatiques H~patlques Pendant Le D~vmentioning

confidence: 99%

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Abnormalities in hepatic enzyme activities during development of diabetes in db mice

Chang

Schneider

1970

Diabetologia

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Summary. Seven hepatic enzymes were assayed in vitro in diabetic and control C57BL/Ks mice at 1, 2, and 41/2 month. An elevation in phosphoenolpyruvate carboxykinase and glueose-6-phosphatase was observed before the onset of hyperglycemia in db mice at the age of 1 month. At two months, these mice had hyperglycemia, hyperinsulinemia aud high levels of phosphoenolpyruvate carboxykinase, glucose-6-phosphatase, fruetose-l,6-diphosphatase, pyruvate kinase and 6-phosphogluconate dehydrogenase. The 41/2 month old db mice had normal plasma insulin, severe hyperglycemia, exorbitant amount of hepatic gluconeogenie enzymes and reduced quantity of glycolytic and pentose-phosphate shunt enzymes. The disturbance in enzyme activities and blood sugar was partially controlled by placing the animals on a limited diet beginning at the age of 1 month. In rive studies indicated that hyperglycemia resulted, at least in part, from an accelerated rate of gluconeogenesis. The development of diabetes in these mice is discussed with reference to these findings. Anomalies d'activit~s enzymatiques h~patlques pendant le d~veloppement du diab~te chez [a souris dbRdsum~. 7 enzymes hdpatiques ont gtd dtudi6s in vibro chez les souris diab@tiques et contr61es de la souehe C57BL/Ks, ~ l'~ge de 1, 2, et 4 mois et demi. Avant l'apparition de l'hyperglyc6mie, une augmentation de la phospho6nolpyruvate carboxykinase et de la glucose-6-phosphatase a dr6 observde chez la souris db agde d'un mois./k l'&ge de 2 reels, cos sourls pr6sentaient une hyperglyc6mie, une hyperinsulin@mie et une activit6 accrue de la phospho6nolpyruvate carboxykinase, de la glucose-6-phosphatase, de la fruetose-l,6-diphosphatase, de la pyruvate kinase et de la 6-phosphogluconate d@liydro-ggnase. Chez los souris db de 4 mois et demi, on a observ6 des taux normaux d'insulindmie, une hyperglycdmie s@v@re, une activit6 extr~mement @levde des enzymes de la glucon6og@n~se h6patique et extr@mement r6duite de ceux de la glycolyse et du cycle des pentoses. Les dgsordres de ces enzymes ainsi que Iceux~ du glucose sanguin ont pu @tre contr61es partielleuent ell soumettaut les animaux ~ une restriction alimentaire d@s l'&ge d'un mois. Des 6tudes in vivo ont indiqu6 que l'hyperglyc6mie r6sulte, ell partie du moins, d'une glucon6o-g@n~se aec@l@r@e. L'apparition du diab&te chez la souris est discut6e ~ la lumi@re de ees r6sultats. Verd~nderungen yon Enzym-Aktlvi~ten der JLeber wdih. rend der Entwiclclung des Diabetes der dbdb MausZusammenfassung. Die Bestlmmung der Aktivit~t yon 7 Enzymen der glykolytischen und gluconeogenetischen Ketten in Leberextrakten yon 1, 2 and 4 ~ ~onate alton db/db l~usen nnd normalen Kontrolltieren ergab folgende Resultate: Bei noch normoglyks db/db ~r im Alter yon 1 l~onat waren Phosphoenolpyruvat. Carboxikinase und Glucose-6-Phosphatase-Aktivitiit erh6ht. Im Alter yon 2 l~onaten (manifesto Hyperglyk~mie und Hyperlnsulingmie) waren auger den Schliisselenzymen der Gluconeogenese auch die A~ivit~ten der Pyruvat Kinase und der 6-Phosphogluconat-Dehydrogenase erh6ht. Be...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Anomalies D'activit~s Enzymatiques H~patlques Pendant Le D~vunclassified

Section: Anomalies D'activit~s Enzymatiques H~patlques Pendant Le D~vmentioning

confidence: 99%

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Abnormalities in hepatic enzyme activities during development of diabetes in db mice

Chang

Schneider

1970

Diabetologia

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“…The disease is therefore most severe and eventually lethal among the Chinese hamsters [1,8] and the C57BL/Ks --db/db mice [i2, 16,17], animals in which a progressive diminution of the beta cell mass eventually leads to insulin insufficiency. In contrast, laboratory models such as the C57BL/6J--ob/ob mice [i8, 19] and the C3Hf X I F 1 (Wellesley hybrid) mice [20, 2i] have greatly enlarged pancreatic islets, with increased numbers of beta cells, an enhanced insulin synthetic capacity and a more mild syndrome.…”

mentioning

confidence: 99%

Studies in the diabetic Chinese hamster: Light microscopy and autoradiography of pancreatic islets

Gerritsen

Dulin

et al. 1974

Diabetologia

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Summary. Light microscopic and autoradiographie studies were performed in normal genetic nondiabetie and diabetic Chinese hamsters after the administration of thymidine-aH and correlated with levels of blood glucose (BG) and plasma insulin (IRI). Pancreatic islets of normal hamsters contained well granulated beta cells; rare islet ceils incorporated thymidine-3H and the IRI/BG ratio (I/G) was = 1.91. l~ecent 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-ketotie 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. Glucoeortieoid 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 glueoeorticoids 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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Morphometric evaluation of diabetes‐associated ovarian atrophy in the C57BL/KsJ mouse: Relationship to age and ovarian function

1985

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Progressive, diabetes-associated ovarian atrophy was analyzed in C57BL/KsJ diabetic (db/db) and control (+/?) mice between 2 and 16 weeks of age. Tissue changes were histologically and morphometrically analyzed and compared with ovarian functional indices (i.e., serum estradiol and progesterone) and metabolic (i.e., glucose uptake and estradiol sequestration) parameters. No significant differences were found between the ovarian follicular populations of either group at 2 and 4 weeks of age. However, between 4 and 8 weeks, the ovaries of diabetic mice exhibited marked stromal and follicular degeneration and an associated decline in the population of viable follicles as compared with controls. Between 8 and 16 weeks of age the follicular atrophy in the diabetics became more marked, as compared with controls, with the accumulation of intracellular lipid pools accenting the tissue degeneration and adiposity observed in both follicular and stromal compartments. In addition, ovarian function was depressed after 6 weeks of age in diabetic females as compared with controls as indicated by lowered serum estradiol and progesterone levels. Ovarian glucose uptake was enhanced in diabetic females while the ability of the ovary to sequester radiolabeled estradiol declined between 4 and 16 weeks of age as compared with controls. These data indicate that ovarian dysfunction in the (db/db) mutant mouse is associated with follicular atrophy, adiposity, impaired steroidogenesis, and imbalanced glucose utilization. These events occur in temporal association with the onset and progressive exacerbation of the hyperglycemic condition. It is suggested that ovarian involution in these mutants is directly related to an impaired follicular ability to metabolize properly the elevated intracellular glucose concentrations that develop in the (db/db) mice as compared with controls.

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Studies with the mutation, diabetes, in the mouse

Cited by 322 publications

References 24 publications

Abnormalities in hepatic enzyme activities during development of diabetes in db mice

Abnormalities in hepatic enzyme activities during development of diabetes in db mice

Studies in the diabetic Chinese hamster: Light microscopy and autoradiography of pancreatic islets

Morphometric evaluation of diabetes‐associated ovarian atrophy in the C57BL/KsJ mouse: Relationship to age and ovarian function

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