Pub Date : 2011-03-28DOI: 10.2174/1876524601104010014
A. Kakehashi
Diabetes is now increasing in not only developed countries but also developing countries. Diabetes is often a difficult problem for patients because of the changes that must be made in lifestyle plus the medications that they must take, but management becomes even more difficult and costly when complications develop. In the early stage of diabetes, many diabetic patients may not pay much attention to their glycemic control. However, after diabetic complications have developed, they experience the symptoms that arise from these complications. In this stage of diabetes, glycemic control may not be sufficient to adequately treat these complications. Furthermore, aggressive glycemic control may sometimes worsen their symptoms such as early worsening of diabetic retinopathy. These diabetic complications severely affect the patient’s quality of life. In order to treat diabetic complications optimally, we should clarify the pathogenic mechanisms underlying them. In order to accomplish this mission, good animal models of diabetic complication are extremely useful. Although many animal model of diabetes have been developed, there are only a few animal models that exhibit diabetic complications. In this context, a newly established non-obese type 2 model rat, the spontaneously diabetic Torii (SDT) rat, is very relevant. At first, the SDT rat was reported as an animal model of severe diabetic retinopathy resembling human diabetic retinopathy. Later, many other diabetic complications were found in this rat. The focus of the present special issue is this novel animal model of diabetic complications: the SDT rat. I hope that the topics presented in this issue will contribute to medical research into the treatment of diabetic complications.
{"title":"Editorial: Novel Animal Model of Diabetic Complications: The SDT Rat","authors":"A. Kakehashi","doi":"10.2174/1876524601104010014","DOIUrl":"https://doi.org/10.2174/1876524601104010014","url":null,"abstract":"Diabetes is now increasing in not only developed countries but also developing countries. Diabetes is often a difficult problem for patients because of the changes that must be made in lifestyle plus the medications that they must take, but management becomes even more difficult and costly when complications develop. In the early stage of diabetes, many diabetic patients may not pay much attention to their glycemic control. However, after diabetic complications have developed, they experience the symptoms that arise from these complications. In this stage of diabetes, glycemic control may not be sufficient to adequately treat these complications. Furthermore, aggressive glycemic control may sometimes worsen their symptoms such as early worsening of diabetic retinopathy. These diabetic complications severely affect the patient’s quality of life. In order to treat diabetic complications optimally, we should clarify the pathogenic mechanisms underlying them. In order to accomplish this mission, good animal models of diabetic complication are extremely useful. Although many animal model of diabetes have been developed, there are only a few animal models that exhibit diabetic complications. In this context, a newly established non-obese type 2 model rat, the spontaneously diabetic Torii (SDT) rat, is very relevant. At first, the SDT rat was reported as an animal model of severe diabetic retinopathy resembling human diabetic retinopathy. Later, many other diabetic complications were found in this rat. The focus of the present special issue is this novel animal model of diabetic complications: the SDT rat. I hope that the topics presented in this issue will contribute to medical research into the treatment of diabetic complications.","PeriodicalId":22762,"journal":{"name":"The Open Diabetes Journal","volume":"98 1","pages":"14"},"PeriodicalIF":0.0,"publicationDate":"2011-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84622739","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2011-03-28DOI: 10.2174/1876524601104010096
M. Shinohara, T. Oikawa, Kahei Sato, Y. Kanazawa
In order to examine the effect of sex hormones on diabetic pathogenesis in female Spontaneously Diabetic Torii (SDT) rats, we performed oophorectomy on female SDT rats, administered female hormones after the oophorectomy, and measured body weight changes, plasma glucose concentration, and pancreatic histopathology. At 26 weeks of age, the body weight was significantly heavier in the oophorectomized group and significantly lighter in the estradiol benzoate (EB) administration group than in the sham-operated control group. Although glucose concentration did not significantly change in the oophorectomized group, it was significantly lower in the EB administration group than in both control and the oophorectomized group. Severe histopathological change was observed in the oophoretomized group but not in the EB administration group. Thus, EB blocked weight gain and pancreatic islet change that was induced by oophoretomy and it also lowered glucose concentration. These results suggest that estrogen plays a preventive role for diabetic pathogenesis in female SDT rats.
{"title":"Effect of Oophorectomy and Estrogen Administration on Diabetic Pathogenesis in Female Spontaneously Diabetic Torii Rats","authors":"M. Shinohara, T. Oikawa, Kahei Sato, Y. Kanazawa","doi":"10.2174/1876524601104010096","DOIUrl":"https://doi.org/10.2174/1876524601104010096","url":null,"abstract":"In order to examine the effect of sex hormones on diabetic pathogenesis in female Spontaneously Diabetic Torii (SDT) rats, we performed oophorectomy on female SDT rats, administered female hormones after the oophorectomy, and measured body weight changes, plasma glucose concentration, and pancreatic histopathology. At 26 weeks of age, the body weight was significantly heavier in the oophorectomized group and significantly lighter in the estradiol benzoate (EB) administration group than in the sham-operated control group. Although glucose concentration did not significantly change in the oophorectomized group, it was significantly lower in the EB administration group than in both control and the oophorectomized group. Severe histopathological change was observed in the oophoretomized group but not in the EB administration group. Thus, EB blocked weight gain and pancreatic islet change that was induced by oophoretomy and it also lowered glucose concentration. These results suggest that estrogen plays a preventive role for diabetic pathogenesis in female SDT rats.","PeriodicalId":22762,"journal":{"name":"The Open Diabetes Journal","volume":"8 1","pages":"96-100"},"PeriodicalIF":0.0,"publicationDate":"2011-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82692124","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2011-03-28DOI: 10.2174/1876524601104010015
E. Shafrir,, Y. Kanazawa
The rats listed here have been extensively studied as animal models of diabetic complications and their pathogenesis. The results of studies with the SHROB, JCR:LAcp and OLETF rats are instructive in understanding macro vascular diseases. The Cohen, GK, SHROB and OLETF rats are model of diabetic kidney disease. The SHROB rat might also be useful for diabetic retinopathy study. The importance of mitochondrial inactivity in diabetes was demonstrated with the ZDF rat. The heterogeneous complication models may be useful to understand pathogenesis, prevention and treatment of complications of diabetes mellitus.
{"title":"Rodent Models of Diabetes and Diabetes Complications","authors":"E. Shafrir,, Y. Kanazawa","doi":"10.2174/1876524601104010015","DOIUrl":"https://doi.org/10.2174/1876524601104010015","url":null,"abstract":"The rats listed here have been extensively studied as animal models of diabetic complications and their pathogenesis. The results of studies with the SHROB, JCR:LAcp and OLETF rats are instructive in understanding macro vascular diseases. The Cohen, GK, SHROB and OLETF rats are model of diabetic kidney disease. The SHROB rat might also be useful for diabetic retinopathy study. The importance of mitochondrial inactivity in diabetes was demonstrated with the ZDF rat. The heterogeneous complication models may be useful to understand pathogenesis, prevention and treatment of complications of diabetes mellitus.","PeriodicalId":22762,"journal":{"name":"The Open Diabetes Journal","volume":"12 1","pages":"15-17"},"PeriodicalIF":0.0,"publicationDate":"2011-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75088346","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2011-03-28DOI: 10.2174/1876524601104010026
T. Masuyama
The Spontaneously Diabetic Torii (SDT) rat is a useful animal model of type 2 diabetes mellitus without obesity. The diabetes in this model manifests as severe hyperglycemia and hypoinsulinemia. However, insulin treatment is not required for survival despite marked hyperglycemia. Pancreatic islets display unique pathologic changes such as hemorrhage and fibrosis before the onset of hyperglycemia as well as marked atrophy. Islet injury is associated with macrophage infiltration of the islets and excess production of nitric oxide. Impaired glucose tolerance results from impaired insulin secretion following by decrease in beta cell mass and glucose-stimulated insulin release from beta cells. Beta cells in these animals have low insulin-secreting capacity in response to glucose stimulation, but retain normal responses to sulfonylurea and incretin. Although insulin resistance is less presented by body composition without obesity, the SDT rat has the potential contributions of hepatic insulin resistance and low energy expenditure to the development of diabetes. This article provides an overview of the pathologic features of pancreatic islets such as beta cell function and possible insulin resistance in SDT rats.
{"title":"Characteristics of Diabetes in the SDT Rat","authors":"T. Masuyama","doi":"10.2174/1876524601104010026","DOIUrl":"https://doi.org/10.2174/1876524601104010026","url":null,"abstract":"The Spontaneously Diabetic Torii (SDT) rat is a useful animal model of type 2 diabetes mellitus without obesity. The diabetes in this model manifests as severe hyperglycemia and hypoinsulinemia. However, insulin treatment is not required for survival despite marked hyperglycemia. Pancreatic islets display unique pathologic changes such as hemorrhage and fibrosis before the onset of hyperglycemia as well as marked atrophy. Islet injury is associated with macrophage infiltration of the islets and excess production of nitric oxide. Impaired glucose tolerance results from impaired insulin secretion following by decrease in beta cell mass and glucose-stimulated insulin release from beta cells. Beta cells in these animals have low insulin-secreting capacity in response to glucose stimulation, but retain normal responses to sulfonylurea and incretin. Although insulin resistance is less presented by body composition without obesity, the SDT rat has the potential contributions of hepatic insulin resistance and low energy expenditure to the development of diabetes. This article provides an overview of the pathologic features of pancreatic islets such as beta cell function and possible insulin resistance in SDT rats.","PeriodicalId":22762,"journal":{"name":"The Open Diabetes Journal","volume":"1 1","pages":"26-29"},"PeriodicalIF":0.0,"publicationDate":"2011-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89921354","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2011-03-28DOI: 10.2174/1876524601104010108
Fumihiko Toyoda, A. Kakehashi, Ayumi Ota, Nozomi Kinoshita, C. Kambara, H. Yamagami, H. Tamemoto, H. Ueba, Y. Dobashi, S. Ishikawa, M. Kawakami, Y. Kanazawa
Advanced glycation end products (AGEs) play important roles in the development of ocular complications in diabetes mellitus. Spontaneously Diabetic Torii (SDT) rats have marked hyperglycemia and severe ocular complications. We evaluated the effect of anti-AGE agents, aminoguanidine and pyridoxamine, and an antioxidant, probucol, on the development of diabetic retinopathy (DR) and cataract in SDT rats. Experiment 1 included five SDT rats treated with aminoguanidine, four SDT rats treated with probucol, and four untreated control SDT rats. After age 55 weeks, we evaluated DR by fluorescein angiomicroscopy and pathological study and cataract by biomicroscopy. Experiment 2 included six SDT rats treated with pyridoxamine, and six SDT rats and 10 non-diabetic normal Sprague-Dawley (SD) rats not treated with pyridoxamine. Retinopathy and cataract were evaluated as in experiment 1. Urinary pentosidine and Maillard reaction product X (MRX) levels were measured for 40 weeks in each group. Experiment 1: Mature cataracts and DR developed in all untreated SDT rats; aminoguanidine prevented cataracts and DR (p<0.05, vs untreated SDT rats). Probucol had no effect. Experiment 2: Mature cataracts developed in all untreated SDT rats (p<0.001 vs normal SD rats (0/10)) and DR developed in 67% (p<0.01, vs normal SD rats (0/10, 0%)). Pyridoxamine did not prevent cataracts (6/6, 100�) or DR (4/6, 37%) (nonsignificant vs untreated SDT rats) in SDT rats. Urinary pentosidine levels were higher in untreated (0.12±0.07 μg/mgCre) and pyridoxamine-treated (0.12±0.05 μg/mgCre) SDT rats than normal SD rats (0.069±0.019 μg/mgCre), but not significantly so. Urinary MRX levels were significantly (p<0.01) lower in normal SD rats (17.5±9.6 μg/mgCre) compared with untreated SDT rats (163.0±107.0 μg/mgCre); pyridoxamine had no effect (149.0±66.5 μg/mgCre) (nonsignificant vs untreated SDT rats). Aminoguanidine but not pyridoxamine and probucol prevents DR and cataracts in SDT rats.
{"title":"Prevention of Proliferative Diabetic Retinopathy and Cataract in SDT Rats with Aminoguanidine, an Anti-Advanced Glycation End Product Agent","authors":"Fumihiko Toyoda, A. Kakehashi, Ayumi Ota, Nozomi Kinoshita, C. Kambara, H. Yamagami, H. Tamemoto, H. Ueba, Y. Dobashi, S. Ishikawa, M. Kawakami, Y. Kanazawa","doi":"10.2174/1876524601104010108","DOIUrl":"https://doi.org/10.2174/1876524601104010108","url":null,"abstract":"Advanced glycation end products (AGEs) play important roles in the development of ocular complications in diabetes mellitus. Spontaneously Diabetic Torii (SDT) rats have marked hyperglycemia and severe ocular complications. We evaluated the effect of anti-AGE agents, aminoguanidine and pyridoxamine, and an antioxidant, probucol, on the development of diabetic retinopathy (DR) and cataract in SDT rats. Experiment 1 included five SDT rats treated with aminoguanidine, four SDT rats treated with probucol, and four untreated control SDT rats. After age 55 weeks, we evaluated DR by fluorescein angiomicroscopy and pathological study and cataract by biomicroscopy. Experiment 2 included six SDT rats treated with pyridoxamine, and six SDT rats and 10 non-diabetic normal Sprague-Dawley (SD) rats not treated with pyridoxamine. Retinopathy and cataract were evaluated as in experiment 1. Urinary pentosidine and Maillard reaction product X (MRX) levels were measured for 40 weeks in each group. Experiment 1: Mature cataracts and DR developed in all untreated SDT rats; aminoguanidine prevented cataracts and DR (p<0.05, vs untreated SDT rats). Probucol had no effect. Experiment 2: Mature cataracts developed in all untreated SDT rats (p<0.001 vs normal SD rats (0/10)) and DR developed in 67% (p<0.01, vs normal SD rats (0/10, 0%)). Pyridoxamine did not prevent cataracts (6/6, 100�) or DR (4/6, 37%) (nonsignificant vs untreated SDT rats) in SDT rats. Urinary pentosidine levels were higher in untreated (0.12±0.07 μg/mgCre) and pyridoxamine-treated (0.12±0.05 μg/mgCre) SDT rats than normal SD rats (0.069±0.019 μg/mgCre), but not significantly so. Urinary MRX levels were significantly (p<0.01) lower in normal SD rats (17.5±9.6 μg/mgCre) compared with untreated SDT rats (163.0±107.0 μg/mgCre); pyridoxamine had no effect (149.0±66.5 μg/mgCre) (nonsignificant vs untreated SDT rats). Aminoguanidine but not pyridoxamine and probucol prevents DR and cataracts in SDT rats.","PeriodicalId":22762,"journal":{"name":"The Open Diabetes Journal","volume":"150 1","pages":"108-113"},"PeriodicalIF":0.0,"publicationDate":"2011-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73461246","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2011-03-28DOI: 10.2174/1876524601104010041
Fumihiko Toyoda, A. Kakehashi, Kana Hashimoto, Nozomi Kinoshita, C. Kanbara, H. Yamagami, H. Tamemoto, S. Ishikawa, Y. Dobashi, M. Kawakami, Y. Kanazawa
Background/Aims: The Spontaneously Diabetic Torii (SDT) rat develops advanced diabetic retinopathy (DR). The aim of this study was to identify advanced glycation end products (AGEs) related to vascular endothelial growth factor (VEGF) expression, a cause of DR in SDT rats. Methods: One eye was obtained from six SDT rats (blood glucose, >250 mg/dl) and 10 nondiabetic normal Sprague- Dawley (SD) rats and prepared for immunohistochemical study of VEGF and AGEs (pyrraline, pentosidine, carboxy methyl lysine (CML)). Immunostaining was described as minimal, moderate, and severe. Results: In diabetic rats, for CML, five eyes had severe and one moderate immunostaining. For pyrraline, one eye had moderate and five eyes minimal immunostaining. For pentosidine, one eye had moderate and five eyes minimal immunostaining. For VEGF, three eyes each had moderate and severe immunostaining. In nondiabetic rats, for CML one eye had minimal, seven had moderate, and two had severe immunostaining. For pyrraline, four eyes had moderate and six eyes minimal immunostaining. For pentosidine, 10 eyes had minimal immunostaining. For VEGF, one eye had moderate and nine had minimal immunostaining. The prevalence rates of CML and VEGF were significantly (P<0.05, P<0.001, respectively) greater in diabetic than in nondiabetic rats. The prevalence rates of pyrraline and pentosidine were not significantly (P=0.35, P=0.38) different between diabetic and nondiabetic rats. Conclusion: CML coexists with VEGF and may be involved in the pathogenesis of severe ocular complications in SDT rats.
{"title":"Accumulation of AGEs and VEGF in Eyes of SDT Rats","authors":"Fumihiko Toyoda, A. Kakehashi, Kana Hashimoto, Nozomi Kinoshita, C. Kanbara, H. Yamagami, H. Tamemoto, S. Ishikawa, Y. Dobashi, M. Kawakami, Y. Kanazawa","doi":"10.2174/1876524601104010041","DOIUrl":"https://doi.org/10.2174/1876524601104010041","url":null,"abstract":"Background/Aims: The Spontaneously Diabetic Torii (SDT) rat develops advanced diabetic retinopathy (DR). The aim of this study was to identify advanced glycation end products (AGEs) related to vascular endothelial growth factor (VEGF) expression, a cause of DR in SDT rats. Methods: One eye was obtained from six SDT rats (blood glucose, >250 mg/dl) and 10 nondiabetic normal Sprague- Dawley (SD) rats and prepared for immunohistochemical study of VEGF and AGEs (pyrraline, pentosidine, carboxy methyl lysine (CML)). Immunostaining was described as minimal, moderate, and severe. Results: In diabetic rats, for CML, five eyes had severe and one moderate immunostaining. For pyrraline, one eye had moderate and five eyes minimal immunostaining. For pentosidine, one eye had moderate and five eyes minimal immunostaining. For VEGF, three eyes each had moderate and severe immunostaining. In nondiabetic rats, for CML one eye had minimal, seven had moderate, and two had severe immunostaining. For pyrraline, four eyes had moderate and six eyes minimal immunostaining. For pentosidine, 10 eyes had minimal immunostaining. For VEGF, one eye had moderate and nine had minimal immunostaining. The prevalence rates of CML and VEGF were significantly (P<0.05, P<0.001, respectively) greater in diabetic than in nondiabetic rats. The prevalence rates of pyrraline and pentosidine were not significantly (P=0.35, P=0.38) different between diabetic and nondiabetic rats. Conclusion: CML coexists with VEGF and may be involved in the pathogenesis of severe ocular complications in SDT rats.","PeriodicalId":22762,"journal":{"name":"The Open Diabetes Journal","volume":"2 1","pages":"41-44"},"PeriodicalIF":0.0,"publicationDate":"2011-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75584201","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2011-03-28DOI: 10.2174/1876524601104010114
Nozomi Kinoshita, A. Kakehashi, Y. Dobashi, R. Ono, Fumihiko Toyoda, C. Kambara, Hiroko Yamagam, Yusuke Kitazume, E. Kobayashi, Y. Osakabe, M. Kudo, M. Kawakami, Y. Kanazawa
We tested the effect of topical nipradilol, an antiglaucoma drug with �- and �-blocker and nitric oxide (NO) donor activities, on the early retinal changes using electron microscopy in Spontaneously Diabetic Torii (SDT) rats. In seven young male SDT rats (17 to 18 weeks old), nipradilol solution was instilled in the right eyes and nipradilol-free base solution in the left eyes three times daily for 3 months. All rats were sacrificed and both eyes were enucleated for electron microscopy at the end of the experiments. All rats had blood glucose levels exceeding 350 mg/dl within 2 weeks after the beginning of the experiment (mean final blood glucose level, 558±100.2 mg/dl). In untreated eyes of young SDT rats, the overall pathological features were almost comparable to those in older SDT rats, although the pinocytotic vesicles and free ribosomes were not as remarkable in the latter. In contrast, in nipradilol-treated eyes of SDT rats, although the basement membrane was thickened, microvilli were seen, and a larger number of electron-dense mitochondria were in the wide cytoplasm. Lipofuscin-like electron-dense granules and lamellated myelin figures also were identified. Nipradilol reduced the early morphologic changes in the endothelial cells, which reflects the metabolically active state of diabetic retinopathy in SDT rats through its action as a NO donor.
{"title":"Effects of Topical Nipradilol on Early Diabetic Retinopathy in SDT Rats","authors":"Nozomi Kinoshita, A. Kakehashi, Y. Dobashi, R. Ono, Fumihiko Toyoda, C. Kambara, Hiroko Yamagam, Yusuke Kitazume, E. Kobayashi, Y. Osakabe, M. Kudo, M. Kawakami, Y. Kanazawa","doi":"10.2174/1876524601104010114","DOIUrl":"https://doi.org/10.2174/1876524601104010114","url":null,"abstract":"We tested the effect of topical nipradilol, an antiglaucoma drug with �- and �-blocker and nitric oxide (NO) donor activities, on the early retinal changes using electron microscopy in Spontaneously Diabetic Torii (SDT) rats. In seven young male SDT rats (17 to 18 weeks old), nipradilol solution was instilled in the right eyes and nipradilol-free base solution in the left eyes three times daily for 3 months. All rats were sacrificed and both eyes were enucleated for electron microscopy at the end of the experiments. All rats had blood glucose levels exceeding 350 mg/dl within 2 weeks after the beginning of the experiment (mean final blood glucose level, 558±100.2 mg/dl). In untreated eyes of young SDT rats, the overall pathological features were almost comparable to those in older SDT rats, although the pinocytotic vesicles and free ribosomes were not as remarkable in the latter. In contrast, in nipradilol-treated eyes of SDT rats, although the basement membrane was thickened, microvilli were seen, and a larger number of electron-dense mitochondria were in the wide cytoplasm. Lipofuscin-like electron-dense granules and lamellated myelin figures also were identified. Nipradilol reduced the early morphologic changes in the endothelial cells, which reflects the metabolically active state of diabetic retinopathy in SDT rats through its action as a NO donor.","PeriodicalId":22762,"journal":{"name":"The Open Diabetes Journal","volume":"25 1","pages":"114-118"},"PeriodicalIF":0.0,"publicationDate":"2011-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86593417","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2011-03-28DOI: 10.2174/1876524601104010055
Y. Mera, T. Ohta, T. Sasase
The impairment of glucose metabolism may lead to type 2 diabetes and the malfunction of lipid metabolism contributing to metabolic syndrome, which increases risk of heart disease, vascular disease, and type 2 diabetes. Our previous study provided evidence for involvement of hepatic glucose metabolic disorder in onset and progress of diabetes in Spontaneously Diabetic Torii (SDT) rats. As it is increasingly important to elucidate the mechanism of onset of diabetes and to develop drugs to prevent diabetic pathological progress, SDT rat should offer a highly useful model of spontaneous diabetic onset for such studies. In addition, abnormality in triglyceride (TG) absorption and impaired lipid catabolism antecedent to hypoinsulinemia/hyperglycemia seem to cause postprandial hypertriglyceridemia in SDT rat; hence, the characteristics of lipid metabolism in SDT rat can be useful in studies of diabetic hypertriglyceridemia and TG metabolism.
{"title":"Glucose and Lipid Metabolism in Spontaneously Diabetic Torii Rat","authors":"Y. Mera, T. Ohta, T. Sasase","doi":"10.2174/1876524601104010055","DOIUrl":"https://doi.org/10.2174/1876524601104010055","url":null,"abstract":"The impairment of glucose metabolism may lead to type 2 diabetes and the malfunction of lipid metabolism contributing to metabolic syndrome, which increases risk of heart disease, vascular disease, and type 2 diabetes. Our previous study provided evidence for involvement of hepatic glucose metabolic disorder in onset and progress of diabetes in Spontaneously Diabetic Torii (SDT) rats. As it is increasingly important to elucidate the mechanism of onset of diabetes and to develop drugs to prevent diabetic pathological progress, SDT rat should offer a highly useful model of spontaneous diabetic onset for such studies. In addition, abnormality in triglyceride (TG) absorption and impaired lipid catabolism antecedent to hypoinsulinemia/hyperglycemia seem to cause postprandial hypertriglyceridemia in SDT rat; hence, the characteristics of lipid metabolism in SDT rat can be useful in studies of diabetic hypertriglyceridemia and TG metabolism.","PeriodicalId":22762,"journal":{"name":"The Open Diabetes Journal","volume":"114 1","pages":"55-59"},"PeriodicalIF":0.0,"publicationDate":"2011-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76823479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2011-03-28DOI: 10.2174/1876524601104010018
M. Shinohara
The Spontaneously Diabetic Torii (SDT) rat is a spontaneous animal model of non-obese Type 2 diabetes (T2D) resembling those of humans, established in 1997. I investigated the clinical features of the SDT rats. The time of onset of glucosuria was different between male and female SDT rats; glucosuria appeared at approximately 20 weeks of age in male rats and at approximately 45 weeks of age in female rats. A cumulative incidence of diabetes of 100% was noted by 40 weeks of age in male rats, while it was only 33.3% even by 65 weeks of age in female rats. The survival rate up to 65 weeks of age was 92.9% in male rats and 97.4% in female rats. The male SDT rats were (1) hyperglycemia and hypoinsulinemia (from 25 weeks of age); (2) a significant increase in urea nitrogen levels, urinary protein excretion and HbA1c levels (from 35 weeks of age); (3) long-term survival without insulin treatment after onset of diabetes; additionally, no obesity was noted in any of the male and female rats. These results indicated that the SDT rat strain described here would serve as useful animal model for studies of non-obese T2D.
{"title":"Establishment and Clinical Features in Spontaneously Diabetic Torii Rat","authors":"M. Shinohara","doi":"10.2174/1876524601104010018","DOIUrl":"https://doi.org/10.2174/1876524601104010018","url":null,"abstract":"The Spontaneously Diabetic Torii (SDT) rat is a spontaneous animal model of non-obese Type 2 diabetes (T2D) resembling those of humans, established in 1997. I investigated the clinical features of the SDT rats. The time of onset of glucosuria was different between male and female SDT rats; glucosuria appeared at approximately 20 weeks of age in male rats and at approximately 45 weeks of age in female rats. A cumulative incidence of diabetes of 100% was noted by 40 weeks of age in male rats, while it was only 33.3% even by 65 weeks of age in female rats. The survival rate up to 65 weeks of age was 92.9% in male rats and 97.4% in female rats. The male SDT rats were (1) hyperglycemia and hypoinsulinemia (from 25 weeks of age); (2) a significant increase in urea nitrogen levels, urinary protein excretion and HbA1c levels (from 35 weeks of age); (3) long-term survival without insulin treatment after onset of diabetes; additionally, no obesity was noted in any of the male and female rats. These results indicated that the SDT rat strain described here would serve as useful animal model for studies of non-obese T2D.","PeriodicalId":22762,"journal":{"name":"The Open Diabetes Journal","volume":"1 1","pages":"18-20"},"PeriodicalIF":0.0,"publicationDate":"2011-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89958554","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2011-03-28DOI: 10.2174/1876524601104010045
T. Ohta, T. Sasase
Diabetic nephropathy is a serious complication of diabetes mellitus, making it essential to develop animal models of diabetic complications to simulate the pathogenesis in humans. We monitored pathobiochemical parameters and histopathological findings of kidneys in male Spontaneously Diabetic Torii (SDT) rats. Renal-related parameters in SDT rats have deteriorated with the progress of diabetes mellitus, and histopathological changes in the renal tubules and the glomeruli were observed with aging. Glycemic control in SDT rats prevented the development of renal lesions. The features of SDT rat indicate its usefulness as an animal model for investigating diabetic nephropathy.
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