The influence of age and dietary conditions on diabetes in the db mouse

Wyse, B. M.; Dulin, W. E.

doi:10.1007/bf01212237

Cited by 86 publications

(48 citation statements)

References 10 publications

(13 reference statements)

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“…A higher than normal amount of these enzymes is already present in the very young db mice, before they show any sign of disturbance in blood glucose, or plasma and pancreatic insulin [4]. This suggests an early involvement of hepatic gluconeogenie enzymes in causing hyperglycemia in the db mice.…”

Section: Discussionmentioning

confidence: 92%

“…2 b). When these mice reached the age of 4 ~ months, they showed severe hyperglycemia, normal plasma insulin, depletion of insulin in pancreas [4] Fig. 2.…”

Section: Resultsmentioning

confidence: 98%

“…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: 97%

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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: 92%

“…2 b). When these mice reached the age of 4 ~ months, they showed severe hyperglycemia, normal plasma insulin, depletion of insulin in pancreas [4] Fig. 2.…”

Section: Resultsmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 97%

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

Chang

Schneider

1970

Diabetologia

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“…In support of this, rodent models of leptin deficiency are characterised by insulin resistance and diabetes [8,9], and leptin treatment lowers blood glucose and insulin levels [10] independent of changes in food intake and body weight [11]. Moreover, leptin administration in both rodents [12,13] and humans [14] ameliorates the severe insulin resistance and diabetes phenotype characteristic of other models of leptin deficiency that are not associated with obesity, such as lipodystrophy, a condition characterised by loss of adipose tissue owing to mutations that impair adipogenesis [15].…”

Section: Leptin Regulation Of Glucose Metabolismmentioning

confidence: 99%

The role of leptin in diabetes: metabolic effects

Meek

Morton

2016

Diabetologia

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While it is well established that the adiposity hormone leptin plays a key role in the regulation of energy homeostasis, growing evidence suggests that leptin is also critical for glycaemic control. In this review we examine the role of the brain in the glucose-lowering actions of leptin and the potential mediators responsible for driving hyperglycaemia in states of uncontrolled insulin-deficient diabetes (uDM). These considerations highlight the possibility of targeting leptin-sensitive pathways as a therapeutic option for the treatment of diabetes. This review summa-

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“…Diabetic db/db mice provide an animal model of type 2 diabetes [7]. The natural progression of diabetes in db/db mice, with initial insulin resistance followed by an insulin-secretion defect [8], is similar to the pathogenesis of type 2 diabetes in humans [9]. Recent studies using perfused working hearts from diabetic db/db mice have demonstrated altered cardiac metabolism and reduced contractile performance [5,6].…”

Section: Introductionmentioning

confidence: 99%

Intracellular sodium increase and susceptibility to ischaemia in hearts from type 2 diabetic db/db mice

et al. 2006

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Aims/hypothesis: An important determinant of sensitivity to ischaemia is altered ion homeostasis, especially disturbances in intracellular Na + Na þ i À Á handling. As no study has so far investigated this in type 2 diabetes, we examined susceptibility to ischaemia-reperfusion in isolated hearts from diabetic db/db and control db/+ mice and determined whether and to what extent the amount of Naincrease during a transient period of ischaemia could contribute to functional alterations upon reperfusion. Methods: Isovolumic hearts were exposed to 30-min global ischaemia and then reperfused. 23Na nuclear magnetic resonance (NMR) spectroscopy was used to monitor Na þ i and 31 P NMR spectroscopy to monitor intracellular pH (pH i ). Results: A higher duration of ventricular tachycardia and the degeneration of ventricular tachycardia into ventricular fibrillation were observed upon reperfusion in db/db hearts. The recovery of left ventricular developed pressure was reduced. The increase in Na þ i induced by ischaemia was higher in db/db hearts than in control hearts, and the rate of pH i recovery was increased during reperfusion. The inhibition of Na + /H + exchange by cariporide significantly reduced Na þ i gain at the end of ischaemia. This was associated with a lower incidence of ventricular tachycardia in both heart groups, and with an inhibition of the degeneration of ventricular tachycardia into ventricular fibrillation in db/db hearts. Conclusions/ interpretation: These findings strongly support the hypothesis that increased Na þ i plays a causative role in the enhanced sensitivity to ischaemia observed in db/db diabetic hearts.

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The influence of age and dietary conditions on diabetes in the db mouse

Cited by 86 publications

References 10 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

The role of leptin in diabetes: metabolic effects

Intracellular sodium increase and susceptibility to ischaemia in hearts from type 2 diabetic db/db mice

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