Spontaneous diabetes-like syndrome in WBN/Kob rats

Nakama, Kazumasa; Shichinohe, Kazuhiro; Kobayashi, Kazuo; Naito, Katsushi; Uchida, Osayuki; Yasuhara, Kazuo; Tobe, Masuo

doi:10.1007/bf02624752

Cited by 81 publications

(45 citation statements)

References 13 publications

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“…In various strains of rat, obesity and insulin resistance secondary to leptin receptor deficiency induce diabetes [7,11,17,19]. Original WBN/Kob male rats spontaneously develop diabetes, although its onset is secondary to chronic pan-pancreatitis [2,13,20,22,24,29]. In contrast, female rats of this strain do not show pancreatitis or diabetes.…”

Section: Introductionmentioning

confidence: 99%

“…In contrast, female rats of this strain do not show pancreatitis or diabetes. Male rats of this strain commonly develop chronic pancreatitis by the age of 3 months [2,13,20,22], while diabetes mellitus (characterized by hyperglycemia, hypoinsulinemia, and glycosuria) occurs at 9 months of age [20,22,29]. In WBN/ Kob-fatty rats, both females and males provide a model of non-insulin-dependent diabetes with obesity [1].…”

Section: Introductionmentioning

confidence: 99%

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The Influence of Dietary Restriction on the Development of Diabetes and Pancreatitis in Female WBN/Kob-Fatty Rats

et al. 2010

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Abstract:Original WBN/Kob male rats commonly develop chronic pancreatitis by the age of 3 months, while diabetes mellitus occurs at 9 months. In contrast, female rats of this strain do not show pancreatitis or diabetes. The WBN/Kob-fatty rat is a homozygous (fa/fa) congenic strain for the fa allele of the leptin receptor gene (Lepr). In WBN/Kob-fatty rats, both females and males provide a model of non-insulin-dependent diabetes with obesity. The leptin receptor fatty gene (Lepr fa ) induces obesity and hyperphagia. In the present study, we examined the effect of dietary restriction on pancreatitis and diabetes in female WBN/Kob-fatty rats. Five female fatty rats comprised a restricted feeding group with paired-feeding from 3 to 13 weeks of age, and five female lean rats comprised a control group with paired-feeding. At 13 weeks of age, two of the five female fatty rats of the control group developed diabetes mellitus, while no female fatty rats of the restricted feeding group developed diabetes mellitus. At this stage, pathological changes of the pancreas were observed in female fatty rats. All female fatty rats showed severe interlobular, intra-lobular and intra-islet fibrosis. In female fatty rats of the restricted feeding group, pathological changes of the pancreas were milder those of the free-feeding fatty group. Although dietary restriction could not completely prevent pancreatitis in female fatty rats, the development of diabetes was inhibited by its reduction of the severity of pancreatitis.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The Influence of Dietary Restriction on the Development of Diabetes and Pancreatitis in Female WBN/Kob-Fatty Rats

et al. 2010

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“…Following such persistent diabetic symptoms, these rats develop renal diabetic complications [28,29] and peripheral motor neuropathy [21], acquire enhanced susceptibility to infections in the urinary tract [21], and show cataracts with high incidence [13,20].…”

Section: Introductionmentioning

confidence: 99%

Diabetic Retinopathy and Choroidal Angiopathy in Diabetic Rats (WBN/Kob)

et al. 2009

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Retinopathy and choroidal angiopathy were both detected in aged male rats of the WBN/Kob strain with sustained diabetes. Hyperglycemia and glucosuria were found starting from 12 months of age and lasted through 24 months of age. Macroscopically, the vitreous body was partially or entirely replaced by white mass in 3 of 9 diabetic males. Histopathologically, the intravitreal white mass consisted of collagen fibers accompanied by numbers of newly formed vessels. Intraretinal angiopathy was accompanied with newly formed vessels, which were observed within the retina in 5 of 9 diabetic males, and marked hyalinization of intraretinal vessels was detected in 6 of 9 males irrespective of the presence of intravitreal neovascularization. Furthermore, hyperglycemia-related choroidal angiopathy was also seen with newly formed blood vessels originating from the choroid penetrating the retinal pigment epithelial layer and invading the retina in 8 of 9 diabetic males. Focal proliferation or degeneration of the pigment epithelial cells was associated in the region with choroidal angiopathy. In females, choroidal vessels slightly raised the pigment epithelial layer; however, they were localized in the choroid. The present study indicates that the WBN/Kob strain of rats is a useful model for both diabetic retinopathy and diabetic choroidal angiopathy.

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“…The spontaneous diabetic syndrome has been reported in aged males of the WBN/Kob rat strain [15][16][17][18][19][20][21][22]. These animals show reduced glucose tolerance at 5 months of age and develop the spontaneous diabetic syndrome around 9 months of age [18].…”

Section: Discussionmentioning

confidence: 99%

Changes in the immunoreactivity of protein gene product (PGP) 9.5 in the cochlea of spontaneously diabetic WBN/Kob rats

1997

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In our previous study, hearing impairment of spontaneously diabetic WBN/Kob rats was first detected as an elevation of the hearing threshold in the auditory brainstem response in animals expressing glucose intolerance, then as a decrease in the number of spiral ganglion cells in the cochlea, and finally as oedematous changes in the stria vascularis [1]. Atrophy of the spiral ganglion was also reported as the most common pathological change in the cochlea of diabetic patients [2]. On the other hand, functional changes in the spiral ganglion cells caused by diabetes mellitus remain to be examined.Protein gene product (PGP) 9.5 is a ubiquitin carboxyl-terminal hydrolase [3] prevalent in cells of neural origin [4][5][6]. Although the functional significance of PGP 9.5 is still unclear, this protein may play an essential role in the ubiquitin-related metabolism in nervous tissues. Recently, PGP 9.5 has been increasingly used as a convenient neural marker in neurophysiological studies [7][8][9][10][11][12]. In the present study, therefore, we examined the immunoreactivity for PGP 9.5 in the spiral ganglion cells of the cochlea in prediabetic and diabetic WBN/Kob rats by an immunohistochemical method with computer-assisted image analysis and compared the results with those obtained from normal age-matched Wistar rats in order to reveal the functional changes in the spiral ganglion cells from a quantitative point of view. Diabetologia (1997) 40: 173-178 Changes in the immunoreactivity of protein gene product (PGP) 9.5 in the cochlea of spontaneously diabetic WBN/Kob rats Summary The mechanism of hearing impairment due to diabetes mellitus was examined in relation to changes in the level of the immunoreaction for the protein gene product 9.5 in the cochlea of spontaneously diabetic WBN/Kob rats. At 7 months (33 weeks) of age, when half of the males of this strain manifest diabetes, male WBN/Kob rats were divided into two groups as follows: one group consisted of prediabetic animals showing slightly decreased tolerance to glucose with a normal plasma concentration of glucose, normal urinary excretion of glucose, and functional hearing impairment (assessed in terms of elevation of hearing threshold). The second group consisted of diabetic animals with glucose intolerance, high plasma glucose level, polyuria, urinary glucose excretion, and more apparent elevation of hearing threshold. According to morphometric analysis of the spiral ganglion, the number of ganglion cells was significantly smaller in both the prediabetic and the diabetic animals than in the age-matched control Wistar rats. The staining intensity for protein gene product 9.5 was increased in some spiral ganglion cells of diabetic animals, but decreased in others according to quantitative immunohistochemical analysis. On the other hand, the immunoreactivity for protein gene product 9.5 was similar in the prediabetic animals to that in the control Wistar rats. These results suggest that numerical and immunohistochemical changes in the spiral ganglion cells r...

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Spontaneous diabetes-like syndrome in WBN/Kob rats

Cited by 81 publications

References 13 publications

The Influence of Dietary Restriction on the Development of Diabetes and Pancreatitis in Female WBN/Kob-Fatty Rats

The Influence of Dietary Restriction on the Development of Diabetes and Pancreatitis in Female WBN/Kob-Fatty Rats

Diabetic Retinopathy and Choroidal Angiopathy in Diabetic Rats (WBN/Kob)

Changes in the immunoreactivity of protein gene product (PGP) 9.5 in the cochlea of spontaneously diabetic WBN/Kob rats

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