Zucker Diabetic Fatty Rat as a Model for Non-insulin-dependent Diabetes Mellitus

Peterson, Richard G.; Shaw, Wayne; Neel, Mary-Ann; Little, Leah A.; Eichberg, Joseph

doi:10.1093/ilar.32.3.16

Cited by 297 publications

(271 citation statements)

References 16 publications

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“…At 6 weeks of age body mass equaled 193.7 ± 1.9 g vs. 147.2 ± 3.3 g (fa/fa vs. control), at 12 weeks 345.0 ± 5.3 g vs. 284.0 ± 10.1 g and at the age of 19 weeks 372.5 ± 5 g vs. 335.4 ± 6.2 g, which is well in accord with recognized values reported in literature for the ZDF model (19,20).…”

Section: Results Animal Characteristicssupporting

confidence: 92%

Adaptations in Mitochondrial Function Parallel, but Fail to Rescue, the Transition to Severe Hyperglycemia and Hyperinsulinemia: A Study in Zucker Diabetic Fatty Rats

Lenaers

Feyter

Hoeks

et al. 2010

Obesity

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Cross‐sectional human studies have associated mitochondrial dysfunction to type 2 diabetes. We chose Zucker diabetic fatty (ZDF) rats as a model of progressive insulin resistance to examine whether intrinsic mitochondrial defects are required for development of type 2 diabetes. Muscle mitochondrial function was examined in 6‐, 12‐, and 19‐week‐old ZDF (fa/fa) and fa/+ control rats (n = 8–10 per group) using respirometry with pyruvate, glutamate, and palmitoyl‐CoA as substrates. Six‐week‐old normoglycemic–hyperinsulinemic fa/fa rats had reduced mitochondrial fat oxidative capacity. Adenosine diphosphate (ADP)‐driven state 3 and carbonyl cyanide p‐trifluoromethoxyphenylhydrazone (FCCP)‐stimulated state uncoupled (state u) respiration on palmitoyl‐CoA were lower compared to controls (62.3 ± 9.5 vs. 119.1 ± 13.8 and 87.8 ± 13.3 vs. 141.9 ± 14.3 nmol O2/mg/min.). Pyruvate oxidation in 6‐week‐old fa/fa rats was similar to controls. Remarkably, reduced fat oxidative capacity in 6‐week‐old fa/fa rats was compensated for by an adaptive increase in intrinsic mitochondrial function at week 12, which could not be maintained toward week 19 (140.9 ± 11.2 and 57.7 ± 9.8 nmol O2/mg/min, weeks 12 and 19, respectively), whereas hyperglycemia had developed (13.5 ± 0.6 and 16.1 ± 0.3 mmol/l, weeks 12 and 19, respectively). This mitochondrial adaptation failed to rescue the progressive development of insulin resistance in fa/fa rats. The transition of prediabetes state toward advanced hyperglycemia and hyperinsulinemia was accompanied by a blunted increase in uncoupling protein‐3 (UCP3). Thus, in ZDF rats insulin resistance develops progressively in the absence of mitochondrial dysfunction. In fact, improved mitochondrial capacity in hyperinsulinemic hyperglycemic rats does not rescue the progression toward advanced stages of insulin resistance.

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Section: Results Animal Characteristicssupporting

confidence: 92%

Adaptations in Mitochondrial Function Parallel, but Fail to Rescue, the Transition to Severe Hyperglycemia and Hyperinsulinemia: A Study in Zucker Diabetic Fatty Rats

Lenaers

Feyter

Hoeks

et al. 2010

Obesity

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“…In contrast, ZF fa/fa rats of both sexes do not develop diabetes during their lifespan when fed a normal chow ad libitum in similar environmental conditions to those used in our investigations [3,15,23], although they show an impaired glucose tolerance and other signs of insulin resistance associated with obesity. We found that SDT fa/fa rats spontaneously developed hyperglycemia after 5 weeks of age in males and after 8 weeks of age in females, the onset of which is markedly earlier than in wild-type and heterozygous rats.…”

Section: Discussionmentioning

confidence: 60%

A Novel Model of Obesity-Related Diabetes: Introgression of the Leprfa Allele of the Zucker Fatty Rat into Nonobese Spontaneously Diabetic Torii (SDT) Rats

Masuyama

Katsuda

Shinohara³

2005

Exp. Anim.

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“…Several kinds of rodent models are now available for research on DM. These include the BioBreeding rat (20), the streptozotocin or alloxan-induced diabetic rat (13), and the non-obese diabetic mouse (8) as models of type 1 diabetes, and the Zucker diabetic fatty rat (17), the BHE (Bureau of Home Economics) rat (4), the Otsuka-Long-Evans-Tokushima fatty rat (10), and the diet-induced diabetic rat or mouse as models of type 2 DM. In the majority of previous studies on diabetic voiding dysfunction, animal models of chemically-induced type 1 DM have been used (5,6,11,12,18).…”

Section: Resultsmentioning

confidence: 99%

Long-term effects of diabetes mellitus on voiding function in a new model of type 2 diabetes mellitus, the Spontaneously Diabetic Torii (SDT) rat

Matsumoto

Torimoto

Matsuyoshi³

et al. 2009

Biomed. Res.

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The spontaneously diabetic Torii (SDT) rat has recently been established as a model of type 2 diabetes mellitus (DM). The usefulness of this rat model for the study of diabetic voiding dysfunction was investigated. Male SDT rats and male Sprague-Dawley (SD) rats were used. Voiding function was evaluated by a metabolic cage study and cystometry. Total voided volume for 24 h, mean voided volume, and urinary frequency for 24 h were significantly greater in SDT rats at the age of 36 weeks. From cystometry mean inter-micturition interval (IMI) was significantly longer in SDT rats at the age of 22 and 36 weeks. In SDT rats mean IMI was significantly longer at the age of 36 weeks than at the age of 22 weeks. Mean voiding pressure was significantly higher in SDT rats at the age of 22 and 36 weeks. In the present study, SDT rats showed typical diabetic voiding dysfunction similar to other diabetic rat models. It was suggested that activity of the bladder afferent pathways is decreased and the urethral relaxation mechanism is impaired in SDT rats. In addition, SDT rats are suitable to study chronic diabetic voiding dysfunction because they survive without insulin treatment for as long as 60 weeks.The number of patients with diabetes mellitus (DM) is increasing all over the world. Approximately 135 million people have type 2 DM worldwide and it affects more people than type 1 DM. Therefore, it is very important to use animal models of type 2 DM to investigate the pathophysiological mechanisms and pharmacological effects from the clinical point of view. Type 2 DM is a multifactorial disease caused by hormonal imbalance between insulin secretion and peripheral insulin sensitivity (1, 2, 15). The Spontaneously Diabetic Torii (SDT) rat is an inbred rat strain established recently from a colony of normal Sprague-Dawley (SD) rats by Torii Pharmaceutical Company (19). Male SDT rats develop hyperglycemia spontaneously without obesity at 20 weeks of age, with an incident rate reaching 100% at 40 weeks of age. The SDT rat is known as a useful model of non-obese type 2 DM, and it can be a very good candidate for an animal model of type 2 DM to investigate diabetic bladder dysfunction. In this study, it was investigated whether the SDT rat is useful as an animal model of type 2 DM for the study of diabetic cystopathy. MATERIALS AND METHODSMale SDT rats were used. Male SD rats were used as controls. Animal care and handling were done in accordance with institutional guidelines and approved by the Institutional Animal Care and Use Committees at

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Zucker Diabetic Fatty Rat as a Model for Non-insulin-dependent Diabetes Mellitus

Cited by 297 publications

References 16 publications

Adaptations in Mitochondrial Function Parallel, but Fail to Rescue, the Transition to Severe Hyperglycemia and Hyperinsulinemia: A Study in Zucker Diabetic Fatty Rats

Adaptations in Mitochondrial Function Parallel, but Fail to Rescue, the Transition to Severe Hyperglycemia and Hyperinsulinemia: A Study in Zucker Diabetic Fatty Rats

A Novel Model of Obesity-Related Diabetes: Introgression of the Leprfa Allele of the Zucker Fatty Rat into Nonobese Spontaneously Diabetic Torii (SDT) Rats

Long-term effects of diabetes mellitus on voiding function in a new model of type 2 diabetes mellitus, the Spontaneously Diabetic Torii (SDT) rat

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