Adenomatous changes and adenocarcinoma of glandular stomach in Wistar rats induced by N-methyl-N′-nitro-N-nitrosoguanidine

Kobori, Oichiro; Gedigk, P.; Totović, V.

doi:10.1007/bf00432467

Cited by 38 publications

(17 citation statements)

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“…[Diabetologia (1995) tional and morphological examinations simultaneously on human subjects. However, we studied WBN/Kob rats which are derived from Wistar rats [14] and develop diabetes spontaneously due to endocrine-exocrine pancreatic insufficiency [15][16][17][18][19]. They begin to excrete odorous urine abundantly at the age of about 9 months, and thereafter show hyperglycaemia and marked intolerance to glucose.…”

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confidence: 99%

Hearing impairment in WBN/Kob rats with spontaneous diabetes mellitus

1995

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SummaryThe inner ear of spontaneously diabetic WBN/Kob rats was functionally and morphologically examined in order to elucidate the relationship between diabetes mellitus and hearing impairment. At 3 months of age, WBN/Kob rats were non-diabetic, and their hearing function was normal. At 6-7 months of age, they showed decreased glucose tolerance and an increasing tendency toward urinary excretion of glucose without high plasma concentration of glucose, and were therefore judged to be pre-diabetic. They also displayed a significant elevation of hearing threshold in the auditory brainstem response, but showed little morphological and histochemical changes in the inner ear. At 12-13 months of age, they were spontaneously diabetic and showed a more apparent elevation of hearing threshold in auditory brainstem response than that in pre-diabetic animals. In addition, they displayed a marked decrease in the number of spiral ganglion cells and oedematous changes in the stria vascularis. The stria vascularis also showed a decrease in the intensity of staining with some lectins, i.e., wheat germ agglutinin, succinylated wheat germ agglutinin, Soranum tuberosum lectin, and concanavalin A. In conclusion, hearing impairment is induced by diabetes in the WBN/ Kob rats first as an elevation of hearing threshold along with glucose intolerance; secondly, as a decrease in the number of spiral ganglion cells; and thirdly, as oedematous change of the stria vascularis with decreased intensity of lectin staining. [Diabetologia (1995) tional and morphological examinations simultaneously on human subjects. However, we studied WBN/Kob rats which are derived from Wistar rats [14] and develop diabetes spontaneously due to endocrine-exocrine pancreatic insufficiency [15][16][17][18][19]. They begin to excrete odorous urine abundantly at the age of about 9 months, and thereafter show hyperglycaemia and marked intolerance to glucose. Since they can survive for a long time after the onset of diabetes without insulin treatment, they are a pertinent animal model for analysis of various aspects of diabetes [20,21]. In the present study, therefore, male WBN/Kob rats with spontaneous diabetes underwent functional, morphological, and histochemical examinations to determine the effects of diabetes on auditory function.

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confidence: 99%

Hearing impairment in WBN/Kob rats with spontaneous diabetes mellitus

1995

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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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“…The etiology of most CP cases is still unclear. Male WBN/Kob rats represent an animal model of CP and diabetes mellitus [3,6,10]. The abnormality initiates at approximately 12 weeks of age with marked fibrosis around the pancreatic ducts and blood vessels.…”

Section: Introductionmentioning

confidence: 99%

Hereditary Pancreatitis Model WBN/Kob Rat Strain Has a Unique Haplotype in the Pdwk1 Region on Chromosome 7

Mori

Chen

et al. 2009

Exp. Anim.

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Abstract:The WBN/Kob rat strain is a hereditary animal model of chronic pancreatitis and diabetes mellitus. The major WBN/Kob loci for pancreatitis (Pdwk1 and Pdwk2) are located on chromosomes 7 and X, respectively. In this study, polymorphisms were sought for candidate genes in the Pdwk1 and Pdwk2 regions. Nucleotide polymorphisms were found in 14 candidate genes examined in the Pdwk1 region. These polymorphisms were not associated with functional changes, and hence were unlikely to be a cause of pancreatitis. Seven nucleotide polymorphisms in three candidate genes, Rac2, Grap2, and Xpnpep3, located within a 3.3-Mb region were not found in 14 other inbred rat strains. These results suggest that WBN/Kob has a unique haplotype block in the chromosomal region contatining Pdwk1. Chronic pancreatitis (CP) is a continuing or recurring inflammatory disease of the pancreas that typically causes pain and leads to irreversible morphological and functional damage [12]. The etiology of most CP cases is still unclear. Male WBN/Kob rats represent an animal model of CP and diabetes mellitus [3,6,10]. The abnormality initiates at approximately 12 weeks of age with marked fibrosis around the pancreatic ducts and blood vessels. Then fibrous tissue gradually and extensively invades the pancreas. The islets are also affected by fibrotic degeneration, leading to an obvious decrease in islet number and size. In addition, inflammatory cells infiltrate and damage tissue around the islets and among adjacent acinar cells. This endocrine-exocrine dysfunction eventually leads to diabetes mellitus at 60-90 weeks of age. The processes leading to pancreatitis in WBN/ Kob have been extensively studied. These studies have revealed the involvement of sex hormones [4,7], imbalances of prolyl hydroxylase and collagenase [2], and autoimmunity [8] in pancreatitis. However, the etiology of pancreatitis in WBN/Kob rats is still unknown. Genetic factors are strongly suspected. Thus, a genetic approach should help to elucidate the fundamental cause of WBN/Kob pancreatitis and diabetes mellitus. Chromosomal mapping of WBN/Kob rats for pancreatitis and diabetes mellitus genes was performed by breeding F 2 hybrid progeny between WBN/Kob and BN [11], and peaks of likely ratio statistical scores for linkage to pancreatitis were observed on two chromosomes. One was a broad peak between D7Rat97 (70.3 cM) and D7Rat4 (80.5 cM) on chromosome 7, and the other was at DXRat103 (37.6 cM) on chromosome X. These loci were designated Pdwk1 and Pdwk2 (pancreatitis and diabetes mellitus in WBN/Kob locus 1 and 2), respectively. Identification of Pdwk1 and Pdwk2 genes should shed new light on pancreatitis mechanisms, and to this -Note-

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Adenomatous changes and adenocarcinoma of glandular stomach in Wistar rats induced by N-methyl-N′-nitro-N-nitrosoguanidine

Cited by 38 publications

References 15 publications

Hearing impairment in WBN/Kob rats with spontaneous diabetes mellitus

Hearing impairment in WBN/Kob rats with spontaneous diabetes mellitus

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

Hereditary Pancreatitis Model WBN/Kob Rat Strain Has a Unique Haplotype in the Pdwk1 Region on Chromosome 7

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