A new genetically obese-hyperglycemic rat (Wistar fatty)

Ikeda, H.; Shino, A.; Matsuo, Takao; Iwatsuka, H.; Suzuoki, Z.

doi:10.2337/diabetes.30.12.1045

Cited by 75 publications

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“…WKY rats exhibit increased fasting glucose, increased glucose in response to restraint stress, and increased glucose and insulin in response to a glucose challenge relative to F344 rats, indicating altered glucose regulation in this strain, as previously reported (Ikeda et al 1981; Katayama et al 1997). The increased insulin in response to a glucose challenge suggests that WKY rats maintain appropriate functioning of pancreatic beta cells and infer a dysfunction at the level of the target tissues.…”

Section: Discussionsupporting

confidence: 83%

“…The WKY rat also exhibits hyperglycemia and hyperinsulinemia in response to a glucose challenge (Katayama et al 1997). In fact, unlike the Zucker fatty rat, when the fa gene is mutated in the WKY rat, these animals not only become obese, but also develop diabetes (Ikeda et al 1981; Zucker and Antoniades 1972), indicating that WKY rats likely harbor diabetes susceptibility alleles. It is not known if the increased HPA activity in this strain is contributing to their hyperglycemia and insulin resistance, or if there is a causal relationship between the hyperglycemia and the depressive behavior.…”

Section: Introductionmentioning

confidence: 99%

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Identification of genetic loci involved in diabetes using a rat model of depression

et al. 2009

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While diabetic patients often present with comorbid depression, the underlying mechanisms linking diabetes and depression are unknown. The Wistar Kyoto (WKY) rat is a well-known animal model of depression and stress hyper-reactivity. In addition, the WKY rat is glucose intolerant and likely harbors diabetes susceptibility alleles. We conducted a quantitative trait loci (QTL) analysis in the segregating F2 population of a WKY × Fischer 344 (F344) inter-cross. We have previously published QTL analyses for depressive behavior and hypothalamic-pituitary-adrenal (HPA) activity in this cross. In the current study, we report results from the QTL analysis for multiple metabolic phenotypes, including fasting glucose, post-restraint stress glucose, post-prandial glucose and insulin, and body weight. We identified multiple QTLs for each trait and many of the QTLs overlap with those previously identified using inbred models of type 2 diabetes (T2D). Significant correlations were found between metabolic traits and HPA axis measures and several metabolic loci overlap with loci previously identified for HPA activity in this F2 intercross, suggesting the genetic mechanisms underlying these traits may be similar. These results indicate that WKY rats harbor diabetes susceptibility alleles and suggest that this strain may be useful for dissecting the underlying genetic mechanisms linking diabetes, HPA activity and depression.

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Section: Discussionsupporting

confidence: 83%

Section: Introductionmentioning

confidence: 99%

Identification of genetic loci involved in diabetes using a rat model of depression

et al. 2009

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“…The fa/fa rat has the potential to become an important animal model of T2D with obesity. Type 2 diabetes (T2D) is a major global health problem, and rapidly increasing in prevalence worldwide [3,9,10,14]. T2D is a multifactorial disease caused by a hormonal imbalance between insulin secretion and peripheral insulin sensitivity [5].…”

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confidence: 99%

Plasma Profiles of Glucose, Insulin and Lipids in the Male WBN/Kob-<i>Lepr<sup>fa</sup></i> Rat, a New Model of Type 2 Diabetes with Obesity

Kaji

Okuno

Ohno-Ichiki

et al. 2012

The Journal of Veterinary Medical Science

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ABSTRACT. Plasma profiles of glucose, insulin and lipids were examined in the male WBN/Kob-Lepr fa (fa/fa) rat, a new model of type 2 diabetes (T2D), in comparison with age-matched original male WBN/Kob (lean) rats. The fa/fa rats developed hypertriglycemia, obesity and hyperglycemia from 5, 7, and 9 weeks of age, respectively. Plasma insulin levels in fa/fa rats were significantly higher than those in lean rats at 5 weeks of age, but after 11 weeks of age gradually declined to the levels in lean rats. HOMA-IR, a measure of insulin resistance status, showed that fa/fa rats had insulin resistance. The fa/fa rat has the potential to become an important animal model of T2D with obesity. Type 2 diabetes (T2D) is a major global health problem, and rapidly increasing in prevalence worldwide [3,9,10,14]. T2D is a multifactorial disease caused by a hormonal imbalance between insulin secretion and peripheral insulin sensitivity [5]. Animal models of T2D are useful to elucidate the pathogenesis of the disease and to evaluate the therapeutic activity of new medications. The currently established rodent T2D models are divided into 2 broad categories: experimentally induced nonspontaneous models, and genetically induced spontaneous models.The WBN/Kob-Lepr fa (fa/fa) rat is a new congenic strain that has been developed by introducing the fa gene of the Zucker fatty (ZF) rat into the original WBN/Kob (lean) rat genome [1,2]. The male, but not female, lean rat is a hereditary model of diabetes mellitus and chronic pancreatitis [13,15]. The leptin receptor fatty gene (Lepr fa ) is a recessive mutation which was reported as a cause of obesity in ZF rats which exhibit hyperphagia resulting from a deficiency of leptin receptor signaling followed by obesity, hyperinsulinemia and dyslipidemia [6,11,16]. The fa/fa rat has been reported as a model of T2D with obesity [1, 2], but little is known about profiles of plasma insulin and lipids in this strain. In order to further characterize the fa/fa rat as a T2D model, we evaluated the plasma profiles of glucose, insulin and lipids in fa/fa rats in comparison with those in lean rats.Male WBN/Kob-Lepr fa (fa/fa) rats and age-matched male WBN/Kob (lean) rats (Japan SLC Inc., Shizuoka, Japan) were used in the present study. The fa/fa rats were confirmed by genotyping of the fa locus, performed according to a PCR-restriction fragment length polymorphism method [8]. The rats were housed in a climate-controlled room with a temperature of 23 ± 3°C, humidity of 55 ± 5%, and 12-hr lighting cycle. A commercial rat chow (CRF-1 ® , Oriental Yeast, Tokyo, Japan) and water were provided ad libitum. All study protocols were approved by the Animal Research Committee of Azabu University.Body weight and plasma levels of glucose, insulin, triglyceride (TG) and non-esterified fatty acids (NEFA) were analyzed in rats from the age of 5 weeks to 19 weeks at 2-week intervals. Blood was collected from the tail vein of non-fasted conscious rats into a heparinized glass capillary, and centrifuged to remove plasma. P...

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“…VMH and ZF rats are most frequently used as models for simple obesity (2,3). In contrast, WF rats, which have been established by transfemng the fa gene of ZF rats to Wistar Kyoto rats, develop both obesity and diabetes (4).…”

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confidence: 99%

Insulin and Glucose Transporter Gene Expression in Obesity and Diabetes

Seino

Yamamoto

Koh

1992

Experimental Biology and Medicine

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In order to determine the role of insulin and glucose transporter gene expression in the development of diabetes in obesity, we examined insulin and GLUT2-liver type and GLUT4-muscle-fat type glucose transporter mRNA levels in obese and diabetic rats. Ventromedial hypothalamus-lesioned (VMH), Zucker fatty (ZF), and Wistar fatty (WF) rats were used as models. VMH and ZF rats are most frequently used as models for simple obesity. In contrast, WF rats, which have been established by transferring the fa gene of ZF rats to Wistar Kyoto rats, develop both obesity and diabetes. Pancreatic insulin content of VMH rats at 10 weeks after the operation and of ZF rats at 5 and 14 weeks of age was significantly higher than that of controls. On the other hand, insulin content of WF rats at 5 and 14 weeks of age was not significantly different from that of lean littermates. The insulin mRNA levels of VMH rats were increased progressively and were significantly higher than those in sham-operated animals at 4 and 10 weeks after the operation. In ZF rats, the insulin mRNA levels at 5 and 14 weeks of age were significantly higher than those of their lean littermates. In WF rats, by contrast, the insulin mRNA levels were similar to those of lean littermates at 5 and 14 weeks of age. The insulin mRNA levels of WF rats were about 40% of that of ZF rats at 14 weeks of age. On the other hand, at 14 weeks of age, the GLUT2 mRNA levels of liver were significantly higher in ZF and WF rats than those in their respective littermates, but not at 5 weeks of age. The GLUT4 mRNA levels of skeletal muscle in both ZF and WF rats were not significantly different from those of controls. It is suggested that the inability of WF rats to augment insulin gene expression in response to a large demand for insulin is associated with the occurrence of diabetes, and that the activation of GLUT2 mRNA without the activation of GLUT4 mRNA is common to obesity with and without diabetes.

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A new genetically obese-hyperglycemic rat (Wistar fatty)

Cited by 75 publications

References 0 publications

Identification of genetic loci involved in diabetes using a rat model of depression

Identification of genetic loci involved in diabetes using a rat model of depression

Plasma Profiles of Glucose, Insulin and Lipids in the Male WBN/Kob-<i>Lepr<sup>fa</sup></i> Rat, a New Model of Type 2 Diabetes with Obesity

Insulin and Glucose Transporter Gene Expression in Obesity and Diabetes

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