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Isao Makino - One of the best experts on this subject based on the ideXlab platform.
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increased levels of advanced glycosylation end products in the kidney and liver from spontaneously diabetic Chinese Hamsters determined by immunochemical assay
Metabolism-clinical and Experimental, 2000Co-Authors: Masaaki Eto, Isao Makino, Atsuko Abiko, Norie Araki, Seikoh HoriuchiAbstract:Increased levels of advanced glycosylation end products (AGEs) have been reported in tissues in association with diabetes mellitus. Thus, we measured tissue AGE levels and detected an accumulation of AGEs in the kidney and liver from spontaneously diabetic Chinese Hamsters (CHAD) to determine the relationship between AGEs and diabetes mellitus. Diabetic CHAD aged 12 to 13 months were studied together with age-matched nondiabetic CHAD. We used an AGE-specific noncompetitive enzyme-linked immunosorbent assay (ELISA) with polyclonal anti-AGE-bovine serum albumin (BSA) antibody to measure tissue AGE levels. The samples extracted from the kidney and liver obtained from diabetic and nondiabetic CHAD reacted with anti-AGE-BSA antibody. When the absorbance of standard AGE-BSA (0.1 μg/mL) was expressed as 1 U, AGE levels in the kidney and liver from diabetic CHAD were significantly increased as compared with nondiabetic CHAD (kidney, 0.26 ± 0.05 v 0.10 ± 0.03 U/μg protein, P v 0.09 ± 0.02 U/μg protein, P P
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natural course of diabetic peripheral neuropathy in spontaneous onset diabetic Chinese Hamsters
Diabetes Research and Clinical Practice, 1995Co-Authors: Fuminori Hirano, Hirotoshi Tanaka, Kensaku Okamoto, Yuichi Makino, Mamoru Inaba, Yoshinobu Nomura, Etsushi Fukawa, Takanori Miura, Takako Tani, Isao MakinoAbstract:We investigated metabolic and pathological changes in the peripheral nerve of the spontaneous-onset diabetic Chinese hamster. Electrophysiological examination revealed that the motor nerve conduction velocity was significantly decreased at 10 months and afterwards, however, the F-wave latency was significantly increased at 5 months and afterwards. Concerning sciatic nerve contents of sorbitol, myo- and scyllo-inositol, the content of sorbitol was not significantly increased at 5 months, but, myo- and scyllo-inositol were significantly decreased at 5 months and thereafter. At 10 and 15 months, however, sciatic nerve content of sorbitol was significantly increased. On morphological examination, loss of large myelinated fiber and reciprocal increase in degenerative fiber were also seen in sciatic nerve, but not in tibial nerve, at 5 months. At 15 months, these morphological changes were also found in the tibial as well as the sciatic nerve. Thus, we may hypothesize that F-wave latency is useful in the detection of initial diabetic neuropathy, and that the initial pathological changes in diabetic neuropathy of diabetic Chinese Hamsters are predominantly found in the proximal site of peripheral nerves.
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natural history of b cell dysfunction in spontaneously diabetic Chinese Hamsters
Diabetes Research and Clinical Practice, 1994Co-Authors: Katsumi Nakajima, Akizuki Morikawa, Isao MakinoAbstract:Abstract To elucidate the pathogenesis of diabetes in spontaneously diabetic Chinese Hamsters (CHAD strain), a longitudinal study from just after weaning to overt diabetic state was performed. Fasting and non-fasting plasma glucose, non-fasting plasma insulin and pancreatic hormone contents (insulin, glucagon and amylin) were measured, and light microscopic examination of pancreatic islets by immunohistochemical technique and pancreas perfusion study were performed. No insulitis was found in the islets of the CHAD strain. In animals aged 1 month, there was no significant difference in the percentage of B-cell area to islet area between the CHAD strain and the control. At this stage, hyperinsulinemia was observed despite normal plasma glucose levels both in fasting and non-fasting states. In the animals of the CHAD strain aged 2–4 months, insulin secretion from the pancreas, pancreatic insulin content and non-fasting plasma insulin level decreased in proportion to the decrease of B-cell mass. In animals aged about ten months, severe hyperglycemia and hypoinsulinemia were observed. We demonstrated the existence of amylin-like immunoreactivity in the B-cells of Chinese Hamsters. However, no amyloid deposit was observed in the islets of the CHAD strain. After the onset of diabetes, amylin secretion from the pancreas and pancreatic amylin content in the CHAD strain were significantly lower than those in the control. We demonstrated the natural history of B-cell dysfunction in the CHAD strain. It could mean the process of B-cell exhaustion. The profile of the CHAD strain is similar to some types of human NIDDM. Therefore, the CHAD strain is a useful diabetic model in the study of NIDDM.
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urinary bladder dysfunction in spontaneously diabetic Chinese Hamsters
Diabetes Research and Clinical Practice, 1994Co-Authors: Hiroshi Itoh, Akizuki Morikawa, Isao MakinoAbstract:Abstract Urinary bladder dysfunction was investigated in spontaneously diabetic Chinese Hamsters of the Asahikawa colony (CHAD). The wet weight of the urinary bladder was significantly increased in CHAD when compared with nondiabetic controls. In response to continuous infusion of physiological saline into the bladder under anesthesia, regular micturition was observed in controls. However, the threshold volume (i.e. the minimum volume at which rhythmic contraction appeared) was significantly increased and the amplitude of bladder contractions during micturition was decreased in CHAD aged 3–5 months (duration of diabetes, 0.6–2.2 months), leading to incomplete micturition. The frequency of micturition was also increased. Overflow incontinence was observed in all CHAD aged 13–15 months (duration of diabetes, 10–14 months). Acetylcholinesterase staining and activity in the urinary bladder walls were both significantly decreased in CHAD compared with controls. The in vitro increment of urinary bladder pressure caused by stimulation with bethanechol was not different between CHAD and controls. These findings suggest that CHAD have urinary bladder dysfunction which is caused by autonomic neuropathy and not by detrusor myopathy.
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peripheral insulin resistance precedes the onset of hyperglycemia in spontaneously diabetic Chinese Hamsters of asahikawa colony
Diabetes Research and Clinical Practice, 1993Co-Authors: Masayuki Takahashi, Masaaki Eto, Isao MakinoAbstract:To investigate the pathogenesis of spontaneously diabetic Chinese Hamsters of Asahikawa colony (CHAD), hepatic glucose production (HGP) and glucose uptake of several tissues were determined before the onset of hyperglycemia (prediabetic state). HGP was calculated as glucose disposal in postabsorptive state using [3-3H]glucose. Glucose uptake of various tissues was assessed as glucose utilization index (R'g) by the 2-deoxyglucose method. Plasma insulin level was increased in prediabetic CHAD but not decreased in CHAD with short-term diabetes compared with control Chinese Hamsters (non-diabetic strain). HGP of prediabetic CHAD was similar to that of control Chinese Hamsters. However, after developing overt hyperglycemia (>200 mg100 ml), HGP increased linearly with plasma glucose level. R'g of adductor longus, extensor digitorum longus and triceps was significantly decreased in prediabetic CHAD. R'g of interscapular brown adipose tissue, white adipose tissue from inguinal, dorsal and epididymal sites were also decreased in prediabetic CHAD. Thus, peripheral insulin resistance precedes the development of hyperglycemia and may be a primary defect in CHAD. No significant difference of R'g in heart ventricle, diaphragm, tibialis anterior or brain was observed. In conclusion, insulin resistance in some muscles and brown and white adipose tissues precedes hyperglycemia and hepatic insulin resistance in CHAD. Hepatic overproduction of glucose (hepatic insulin resistance) is a major factor responsible for overt basal hyperglycemia and may play an important role in developing further diabetic state.
Akizuki Morikawa - One of the best experts on this subject based on the ideXlab platform.
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natural history of b cell dysfunction in spontaneously diabetic Chinese Hamsters
Diabetes Research and Clinical Practice, 1994Co-Authors: Katsumi Nakajima, Akizuki Morikawa, Isao MakinoAbstract:Abstract To elucidate the pathogenesis of diabetes in spontaneously diabetic Chinese Hamsters (CHAD strain), a longitudinal study from just after weaning to overt diabetic state was performed. Fasting and non-fasting plasma glucose, non-fasting plasma insulin and pancreatic hormone contents (insulin, glucagon and amylin) were measured, and light microscopic examination of pancreatic islets by immunohistochemical technique and pancreas perfusion study were performed. No insulitis was found in the islets of the CHAD strain. In animals aged 1 month, there was no significant difference in the percentage of B-cell area to islet area between the CHAD strain and the control. At this stage, hyperinsulinemia was observed despite normal plasma glucose levels both in fasting and non-fasting states. In the animals of the CHAD strain aged 2–4 months, insulin secretion from the pancreas, pancreatic insulin content and non-fasting plasma insulin level decreased in proportion to the decrease of B-cell mass. In animals aged about ten months, severe hyperglycemia and hypoinsulinemia were observed. We demonstrated the existence of amylin-like immunoreactivity in the B-cells of Chinese Hamsters. However, no amyloid deposit was observed in the islets of the CHAD strain. After the onset of diabetes, amylin secretion from the pancreas and pancreatic amylin content in the CHAD strain were significantly lower than those in the control. We demonstrated the natural history of B-cell dysfunction in the CHAD strain. It could mean the process of B-cell exhaustion. The profile of the CHAD strain is similar to some types of human NIDDM. Therefore, the CHAD strain is a useful diabetic model in the study of NIDDM.
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urinary bladder dysfunction in spontaneously diabetic Chinese Hamsters
Diabetes Research and Clinical Practice, 1994Co-Authors: Hiroshi Itoh, Akizuki Morikawa, Isao MakinoAbstract:Abstract Urinary bladder dysfunction was investigated in spontaneously diabetic Chinese Hamsters of the Asahikawa colony (CHAD). The wet weight of the urinary bladder was significantly increased in CHAD when compared with nondiabetic controls. In response to continuous infusion of physiological saline into the bladder under anesthesia, regular micturition was observed in controls. However, the threshold volume (i.e. the minimum volume at which rhythmic contraction appeared) was significantly increased and the amplitude of bladder contractions during micturition was decreased in CHAD aged 3–5 months (duration of diabetes, 0.6–2.2 months), leading to incomplete micturition. The frequency of micturition was also increased. Overflow incontinence was observed in all CHAD aged 13–15 months (duration of diabetes, 10–14 months). Acetylcholinesterase staining and activity in the urinary bladder walls were both significantly decreased in CHAD compared with controls. The in vitro increment of urinary bladder pressure caused by stimulation with bethanechol was not different between CHAD and controls. These findings suggest that CHAD have urinary bladder dysfunction which is caused by autonomic neuropathy and not by detrusor myopathy.
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polyol pathway in tissues of spontaneously diabetic Chinese Hamsters cricetulus griseus and the effect of an aldose reductase inhibitor ono 2235
Comparative Biochemistry and Physiology B, 1991Co-Authors: Masatomo Sekiguchi, Kiyoshi Watanabe, Masaaki Eto, Yasunori Iwashima, Akizuki Morikawa, Masayuki Takahashi, Kanbo Ishii, Isao MakinoAbstract:Abstract 1. 1. Sorbitol and fructose levels were significantly elevated in the lens, the sciatic nerve, the retina and the kidney of diabetic Chinese Hamsters and inositol level was significantly decreased in the lens and sciatic nerve of diabetics. 2. 2. The activity of an aldose reductase in the kidney was not different between normal and diabetic Chinese Hamsters. 3. 3. An aldose reductase inhibitor (ONO-2235) had no effect in sorbitol, fructose and inositol contents of all these tissues from diabetic Chinese Hamsters. 4. 4. These results suggest that diabetic Chinese Hamsters produce polyol accumulation in tissues but that there is a clear species-specific difference to inhibition of aldose reductase.
Hiroshi Itoh - One of the best experts on this subject based on the ideXlab platform.
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urinary bladder dysfunction in spontaneously diabetic Chinese Hamsters
Diabetes Research and Clinical Practice, 1994Co-Authors: Hiroshi Itoh, Akizuki Morikawa, Isao MakinoAbstract:Abstract Urinary bladder dysfunction was investigated in spontaneously diabetic Chinese Hamsters of the Asahikawa colony (CHAD). The wet weight of the urinary bladder was significantly increased in CHAD when compared with nondiabetic controls. In response to continuous infusion of physiological saline into the bladder under anesthesia, regular micturition was observed in controls. However, the threshold volume (i.e. the minimum volume at which rhythmic contraction appeared) was significantly increased and the amplitude of bladder contractions during micturition was decreased in CHAD aged 3–5 months (duration of diabetes, 0.6–2.2 months), leading to incomplete micturition. The frequency of micturition was also increased. Overflow incontinence was observed in all CHAD aged 13–15 months (duration of diabetes, 10–14 months). Acetylcholinesterase staining and activity in the urinary bladder walls were both significantly decreased in CHAD compared with controls. The in vitro increment of urinary bladder pressure caused by stimulation with bethanechol was not different between CHAD and controls. These findings suggest that CHAD have urinary bladder dysfunction which is caused by autonomic neuropathy and not by detrusor myopathy.
Chenyang Wang - One of the best experts on this subject based on the ideXlab platform.
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small intestine proteomics coupled with serum metabolomics reveal disruption of amino acid metabolism in Chinese Hamsters with type 2 diabetes mellitus
Journal of Proteomics, 2020Co-Authors: Chenyang Wang, Ruihu Zhang, Wentao Wang, Zeya Shi, Yu Liu, Guohua Song, Hailong Wang, Naijian Han, Liqun Huang, Shouyuan TianAbstract:Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by hyperglycemia, with metabolic disturbances resulting from defects in insulin secretion, insulin resistance (IR), or both. Chinese Hamsters have potential value as non-obese animal models of spontaneous T2DM for studying the pathogenesis and molecular characteristics of diabetes. In this study, the molecular characteristics of the Chinese hamster diabetes animal model were investigated through small intestine proteomics and serum metabolomics. A total of 213 differentially abundant proteins and 14 differentially abundant metabolites were identified through liquid chromatography-tandem mass spectrometry (LC-MS/MS) and gas chromatography-time of flight mass spectrometry (GC-TOF/MS) analysis, respectively. Annotation by bioinformatics analysis revealed that these differentially abundant proteins in the small intestine were commonly associated with abnormal glucose and lipid metabolism, IR, impaired insulin secretion, amino acid metabolism disorders, and inflammatory dysregulation. Moreover, differentially abundant metabolites in the serum were amino acids and were related to diabetic IR. Through the analysis of small intestine proteomics and serum metabolomics in the Chinese hamster diabetes model, we provide a preliminary understanding of the diabetic characteristics of this model from a molecular perspective. This study provides data incentivizing the popularization and application of Chinese Hamsters in T2DM research. SIGNIFICANCE: Spontaneous rodent models of diabetes, such as Chinese Hamsters, effectively summarizes the clinical characteristics of type 2 diabetes and has high applicative value for studying the pathophysiology of diabetes. In order to explore the potential value of the Chinese hamster diabetes animal model in the study of the T2DM molecular mechanism, we performed small intestine proteomic analysis and serum metabolomic analysis in Chinese Hamsters for the first time. After an integrated analysis of proteomics and metabolomics, we have a preliminary understanding of the diabetic characteristics of this model from a molecular perspective. Further, we found that in the occurrence and development of T2DM, the metabolic abnormalities of this model are particularly prominent, especially the metabolism of amino acids. These findings not only provide basic data in support of the popularization and application of the current model in T2DM research, but also provide a new perspective for the exploration of mechanisms related to T2DM.
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phenotypic characterization of a novel type 2 diabetes animal model in a shanxi mu colony of Chinese Hamsters
Endocrine, 2019Co-Authors: Lu Wang, Chenyang Wang, Ruihu Zhang, Yu Liu, Guohua Song, Chunfang Wang, Zhaoyang ChenAbstract:Developing animal models for human diseases is critical for studying complex diseases such as type 2 diabetes mellitus (T2DM). Since inbred colonies of Chinese Hamsters tend toward spontaneous development of diabetes, we investigated them as a possible model. We regarded individuals with fasting blood glucose (FBG) higher than 6.0 mmol/L and post-prandial blood glucose (PBG) higher than 7.0 mmol/L as diabetic based on the mean and 95% frequency distribution values of FBG and PBG. Diabetic Hamsters were characterized based on metabolic profiles, histopathological features, and changes in the expression of genes involved in glucose and lipid metabolism. Metabolic analyses showed that diabetic Hamsters exhibited mild hyperglycemia, hypertriglyceridemia, glucose intolerance, and insulin resistance. Histopathological analysis revealed that cell nuclei migrated inward in skeletal muscle and obvious partial liver lipid deposition and focal necrosis was found. We additionally observed mild injury, atrophy, and occasional vacuolization in islet cells. Changes in the expression of several genes related to glucose and lipid metabolism were observed. Decreased expression of adiponectin and GLUT4 and increased expression of PPARγ, Akt, and leptin was observed in skeletal muscle. Decreased expression of adiponectin with increased expression of PPARγ and leptin was observed in the liver. These results indicate that we have established a spontaneous diabetic hamster line that closely mimics human T2DM, which may hold potential for further research on the pathogenesis and treatment of this disease.
Ruihu Zhang - One of the best experts on this subject based on the ideXlab platform.
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small intestine proteomics coupled with serum metabolomics reveal disruption of amino acid metabolism in Chinese Hamsters with type 2 diabetes mellitus
Journal of Proteomics, 2020Co-Authors: Chenyang Wang, Ruihu Zhang, Wentao Wang, Zeya Shi, Yu Liu, Guohua Song, Hailong Wang, Naijian Han, Liqun Huang, Shouyuan TianAbstract:Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by hyperglycemia, with metabolic disturbances resulting from defects in insulin secretion, insulin resistance (IR), or both. Chinese Hamsters have potential value as non-obese animal models of spontaneous T2DM for studying the pathogenesis and molecular characteristics of diabetes. In this study, the molecular characteristics of the Chinese hamster diabetes animal model were investigated through small intestine proteomics and serum metabolomics. A total of 213 differentially abundant proteins and 14 differentially abundant metabolites were identified through liquid chromatography-tandem mass spectrometry (LC-MS/MS) and gas chromatography-time of flight mass spectrometry (GC-TOF/MS) analysis, respectively. Annotation by bioinformatics analysis revealed that these differentially abundant proteins in the small intestine were commonly associated with abnormal glucose and lipid metabolism, IR, impaired insulin secretion, amino acid metabolism disorders, and inflammatory dysregulation. Moreover, differentially abundant metabolites in the serum were amino acids and were related to diabetic IR. Through the analysis of small intestine proteomics and serum metabolomics in the Chinese hamster diabetes model, we provide a preliminary understanding of the diabetic characteristics of this model from a molecular perspective. This study provides data incentivizing the popularization and application of Chinese Hamsters in T2DM research. SIGNIFICANCE: Spontaneous rodent models of diabetes, such as Chinese Hamsters, effectively summarizes the clinical characteristics of type 2 diabetes and has high applicative value for studying the pathophysiology of diabetes. In order to explore the potential value of the Chinese hamster diabetes animal model in the study of the T2DM molecular mechanism, we performed small intestine proteomic analysis and serum metabolomic analysis in Chinese Hamsters for the first time. After an integrated analysis of proteomics and metabolomics, we have a preliminary understanding of the diabetic characteristics of this model from a molecular perspective. Further, we found that in the occurrence and development of T2DM, the metabolic abnormalities of this model are particularly prominent, especially the metabolism of amino acids. These findings not only provide basic data in support of the popularization and application of the current model in T2DM research, but also provide a new perspective for the exploration of mechanisms related to T2DM.
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phenotypic characterization of a novel type 2 diabetes animal model in a shanxi mu colony of Chinese Hamsters
Endocrine, 2019Co-Authors: Lu Wang, Chenyang Wang, Ruihu Zhang, Yu Liu, Guohua Song, Chunfang Wang, Zhaoyang ChenAbstract:Developing animal models for human diseases is critical for studying complex diseases such as type 2 diabetes mellitus (T2DM). Since inbred colonies of Chinese Hamsters tend toward spontaneous development of diabetes, we investigated them as a possible model. We regarded individuals with fasting blood glucose (FBG) higher than 6.0 mmol/L and post-prandial blood glucose (PBG) higher than 7.0 mmol/L as diabetic based on the mean and 95% frequency distribution values of FBG and PBG. Diabetic Hamsters were characterized based on metabolic profiles, histopathological features, and changes in the expression of genes involved in glucose and lipid metabolism. Metabolic analyses showed that diabetic Hamsters exhibited mild hyperglycemia, hypertriglyceridemia, glucose intolerance, and insulin resistance. Histopathological analysis revealed that cell nuclei migrated inward in skeletal muscle and obvious partial liver lipid deposition and focal necrosis was found. We additionally observed mild injury, atrophy, and occasional vacuolization in islet cells. Changes in the expression of several genes related to glucose and lipid metabolism were observed. Decreased expression of adiponectin and GLUT4 and increased expression of PPARγ, Akt, and leptin was observed in skeletal muscle. Decreased expression of adiponectin with increased expression of PPARγ and leptin was observed in the liver. These results indicate that we have established a spontaneous diabetic hamster line that closely mimics human T2DM, which may hold potential for further research on the pathogenesis and treatment of this disease.