The Experts below are selected from a list of 66 Experts worldwide ranked by ideXlab platform
Kok-onn Lee - One of the best experts on this subject based on the ideXlab platform.
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thymosin beta 4 ameliorates hyperglycemia and improves insulin resistance of KK cg ay j Mouse
Diabetes Research and Clinical Practice, 2012Co-Authors: Jian Zhu, Kok-onn LeeAbstract:Abstract Object To evaluate the efficacy of thymosin beta 4 (Tβ 4 ) on hyperglycemia and insulin sensitivity in a Mouse model of type 2 diabetes mellitus (T2DM). Methods KK mice were divided into the following groups: KK control group, with saline treatment; KK Tβ 4 group, with daily Tβ 4 100ng/10g body weight intraperitoneal injection for 12 weeks. Non-diabetic C57BL mice were used as normal control. OGTT, plasma insulin, HbA1c, serum adiponectin, Tβ 4 , cholesterol, and triglyceride were measured before and after Tβ 4 treatment. The phosphorylated AKT and total AKT protein levels of skeletal muscle from all groups were determined. Results After Tβ 4 treatment, repeat OGTT showed a significant decrease in glucose profiles in the KK Tβ 4 group compared with the KK control group. The KK-Tβ 4 group had reduced mean HbA1c and triglyceride levels, and increased adiponectin compared with KK control group. C57BL mice showed normal glucose homeostasis. The phosphorylated AKT levels of skeletal muscle were significantly increased in KK Tβ 4 group compared with KK control group after glucose stimulation. C57BL mice showed no changes in phosphorylated AKT levels after Tβ 4 treatment. Conclusions Tβ 4 improved glucose intolerance and ameliorated insulin resistance in KK Mouse. Tβ 4 may be a potential alternative insulin sensitizer for treatment of T2DM.
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Thymosin beta 4 ameliorates hyperglycemia and improves insulin resistance of KK Cg-Ay/J Mouse.
Diabetes research and clinical practice, 2012Co-Authors: Jian Zhu, Kok-onn LeeAbstract:To evaluate the efficacy of thymosin beta 4 (Tβ(4)) on hyperglycemia and insulin sensitivity in a Mouse model of type 2 diabetes mellitus (T2DM). KK mice were divided into the following groups: KK control group, with saline treatment; KK Tβ(4) group, with daily Tβ(4) 100ng/10g body weight intraperitoneal injection for 12 weeks. Non-diabetic C57BL mice were used as normal control. OGTT, plasma insulin, HbA1c, serum adiponectin, Tβ(4), cholesterol, and triglyceride were measured before and after Tβ(4) treatment. The phosphorylated AKT and total AKT protein levels of skeletal muscle from all groups were determined. After Tβ(4) treatment, repeat OGTT showed a significant decrease in glucose profiles in the KK Tβ(4) group compared with the KK control group. The KK-Tβ(4) group had reduced mean HbA1c and triglyceride levels, and increased adiponectin compared with KK control group. C57BL mice showed normal glucose homeostasis. The phosphorylated AKT levels of skeletal muscle were significantly increased in KK Tβ(4) group compared with KK control group after glucose stimulation. C57BL mice showed no changes in phosphorylated AKT levels after Tβ(4) treatment. Tβ(4) improved glucose intolerance and ameliorated insulin resistance in KK Mouse. Tβ(4) may be a potential alternative insulin sensitizer for treatment of T2DM. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.
Jian Zhu - One of the best experts on this subject based on the ideXlab platform.
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thymosin beta 4 ameliorates hyperglycemia and improves insulin resistance of KK cg ay j Mouse
Diabetes Research and Clinical Practice, 2012Co-Authors: Jian Zhu, Kok-onn LeeAbstract:Abstract Object To evaluate the efficacy of thymosin beta 4 (Tβ 4 ) on hyperglycemia and insulin sensitivity in a Mouse model of type 2 diabetes mellitus (T2DM). Methods KK mice were divided into the following groups: KK control group, with saline treatment; KK Tβ 4 group, with daily Tβ 4 100ng/10g body weight intraperitoneal injection for 12 weeks. Non-diabetic C57BL mice were used as normal control. OGTT, plasma insulin, HbA1c, serum adiponectin, Tβ 4 , cholesterol, and triglyceride were measured before and after Tβ 4 treatment. The phosphorylated AKT and total AKT protein levels of skeletal muscle from all groups were determined. Results After Tβ 4 treatment, repeat OGTT showed a significant decrease in glucose profiles in the KK Tβ 4 group compared with the KK control group. The KK-Tβ 4 group had reduced mean HbA1c and triglyceride levels, and increased adiponectin compared with KK control group. C57BL mice showed normal glucose homeostasis. The phosphorylated AKT levels of skeletal muscle were significantly increased in KK Tβ 4 group compared with KK control group after glucose stimulation. C57BL mice showed no changes in phosphorylated AKT levels after Tβ 4 treatment. Conclusions Tβ 4 improved glucose intolerance and ameliorated insulin resistance in KK Mouse. Tβ 4 may be a potential alternative insulin sensitizer for treatment of T2DM.
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Thymosin beta 4 ameliorates hyperglycemia and improves insulin resistance of KK Cg-Ay/J Mouse.
Diabetes research and clinical practice, 2012Co-Authors: Jian Zhu, Kok-onn LeeAbstract:To evaluate the efficacy of thymosin beta 4 (Tβ(4)) on hyperglycemia and insulin sensitivity in a Mouse model of type 2 diabetes mellitus (T2DM). KK mice were divided into the following groups: KK control group, with saline treatment; KK Tβ(4) group, with daily Tβ(4) 100ng/10g body weight intraperitoneal injection for 12 weeks. Non-diabetic C57BL mice were used as normal control. OGTT, plasma insulin, HbA1c, serum adiponectin, Tβ(4), cholesterol, and triglyceride were measured before and after Tβ(4) treatment. The phosphorylated AKT and total AKT protein levels of skeletal muscle from all groups were determined. After Tβ(4) treatment, repeat OGTT showed a significant decrease in glucose profiles in the KK Tβ(4) group compared with the KK control group. The KK-Tβ(4) group had reduced mean HbA1c and triglyceride levels, and increased adiponectin compared with KK control group. C57BL mice showed normal glucose homeostasis. The phosphorylated AKT levels of skeletal muscle were significantly increased in KK Tβ(4) group compared with KK control group after glucose stimulation. C57BL mice showed no changes in phosphorylated AKT levels after Tβ(4) treatment. Tβ(4) improved glucose intolerance and ameliorated insulin resistance in KK Mouse. Tβ(4) may be a potential alternative insulin sensitizer for treatment of T2DM. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.
Yuichi Sugiyama - One of the best experts on this subject based on the ideXlab platform.
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pharmacokinetic stereoselectivity of troglitazone an antidiabetic agent in the KK Mouse
Biopharmaceutics & Drug Disposition, 1997Co-Authors: Takashi Izumi, S. Enomoto, K. Hoshiyama, Kunihiro Sasahara, Yuichi SugiyamaAbstract:Troglitazone, an oral antidiabetic agent, is an equal mixture of four stereoisomers involving two asymmetric centres. In the present study, the stereoselectivity of in vitro epimerization in plasma and organ homogenate and in vivo plasma disposition in the KK Mouse, an animal model of non-insulin-dependent diabetes, was examined. In the incubation experiments at 37 °C, there was a fivefold to eightfold acceleration of epimerization at the 5 position of the thiazolidine ring in KK Mouse plasma compared with that in buffer. However, no inversion at the 2 position of the chroman ring was observed. In addition, there was an approximately 1·3-fold difference in the epimerization rates among stereoisomers at the 2 position of the chroman ring. However, there were no differences in the values of the equilibrium constants of epimerization, and the ratio of epimerization among stereoisomers at the 5 position of thiazolidine ring was almost unity. The acceleration of epimerization is thought to be due to the high degree of protein binding because of the relationship between the initial epimerization rate and the dilution ratio of the plasma. Although acceleration of epimerization was also observed in the 20% homogenates of liver, kidney, and intestine of the KK Mouse, the degree of stereoselectivity was lower than in plasma. The analysis of the plasma disposition after intravenous administration of troglitazone stereoisomers, using a kinetic model, indicated that the metabolic clearance in the liver showed a 2·5-fold maximum difference among stereoisomers and that the stereoselectivity of epimerization was low. ©1997 by John Wiley & Sons, Ltd.
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Pharmacokinetic stereoselectivity of troglitazone, an antidiabetic agent, in the KK Mouse.
Biopharmaceutics & drug disposition, 1997Co-Authors: Takashi Izumi, S. Enomoto, K. Hoshiyama, Kunihiro Sasahara, Yuichi SugiyamaAbstract:Troglitazone, an oral antidiabetic agent, is an equal mixture of four stereoisomers involving two asymmetric centres. In the present study, the stereoselectivity of in vitro epimerization in plasma and organ homogenate and in vivo plasma disposition in the KK Mouse, an animal model of non-insulin-dependent diabetes, was examined. In the incubation experiments at 37 degrees C, there was a fivefold to eightfold acceleration of epimerization at the 5 position of the thiazolidine ring in KK Mouse plasma compared with that in buffer. However, no inversion at the 2 position of the chroman ring was observed. In addition, there was an approximately 1.3-fold difference in the epimerization rates among stereoisomers at the 2 position of the chroman ring. However, there were no differences in the values of the equilibrium constants of epimerization, and the ratio of epimerization among stereoisomers at the 5 position of thiazolidine ring was almost unity. The acceleration of epimerization is thought to be due to the high degree of protein binding because of the relationship between the initial epimerization rate and the dilution ratio of the plasma. Although acceleration of epimerization was also observed in the 20% homogenates of liver, kidney, and intestine of the KK Mouse, the degree of stereoselectivity was lower than in plasma. The analysis of the plasma disposition after intravenous administration of troglitazone stereoisomers, using a kinetic model, indicated that the metabolic clearance in the liver showed a 2.5-fold maximum difference among stereoisomers and that the stereoselectivity of epimerization was low.
Jun-ichi Suto - One of the best experts on this subject based on the ideXlab platform.
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The Ay allele at the agouti locus reduces the size and alters the shape of the mandible in mice.
Proceedings of the Japan Academy. Series B Physical and biological sciences, 2009Co-Authors: Jun-ichi SutoAbstract:To confirm my previous findings that the A(y) allele at the agouti locus reduced the mandible size and therefore altered the mandible shape in a KK Mouse strain background, I further investigated the effects of the A(y) allele on mandible morphology on different strain backgrounds, DDD and B6. Principal component analysis revealed that the mandible was significantly smaller in A(y) mice (DDD-A(y) and B6-A(y)) than in corresponding non-A(y) mice (DDD and B6, respectively). Discriminant and canonical discriminant analyses revealed that most mice were classified correctly in their own strains, and misclassification was not observed between DDD (-A(y)) and B6 (-A(y)). The results confirmed that the A(y) allele reduced the mandible size and altered the mandible shape regardless of the strain background. However, the difference in mandible morphology between A(y) mice and the corresponding non-A(y) mice within a strain was not as large as that which intrinsically underlay the two strains. Possible mechanisms of the A(y) action are discussed.
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Genetic analysis of non-insulin-dependent diabetes mellitus in KK and KK-Ay mice
European journal of endocrinology, 1998Co-Authors: Jun-ichi Suto, Saori Matsuura, Kenkichi Imamura, Harumichi Yamanaka, Kenji SekikawaAbstract:The KK Mouse is considered suitable as a polygenic model for human non-insulin-dependent diabetes mellitus. To identify the quantitative trait loci (QTLs) responsible for hyperglycemia and impaired glucose tolerance in KK mice, linkage analysis using 97 microsatellite markers was carried out in a 192 F2 progeny, comprising 93 mice with the a/a genotype at the agouti locus (chromosome 2) and 99 mice with the Ay/a genotype, produced by a cross between a C57BL/6J female and a KK-Ay (Ay congenic) male. In F2 a/a progenies, we identified a QTL for fasting glucose levels on chromosome 6 (LOD score 6.0) and three loci with suggestive linkage on chromosomes 3, 5 and 14, but could not identify loci accounting for glucose tolerance and plasma insulin levels. In F2 Ay/a progenies, there were no loci with statistically significant linkage, but three suggestive loci were identified: a locus for fasting glucose on chromosome 9, and two loci for glucose tolerance on chromosomes 1 and 8. It would thus appear that. although the fasting glucose level is controlled by QTLs in KK mice, these QTLs may be masked by the strong hyperglycemic influence of the Ay allele. Suggestive loci accounting for glucose tolerance may interact with the Ay allele, since these loci were identified only in F2 Ay/a progeny. This is consistent with the finding that the impaired glucose tolerance in KK mice is moderate and becomes overt when associated with the Ay allele.
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Genetics of obesity in KK Mouse and effects of A(y) allele on quantitative regulation.
Mammalian genome : official journal of the International Mammalian Genome Society, 1998Co-Authors: Jun-ichi Suto, Saori Matsuura, Kenkichi Imamura, Harumichi Yamanaka, Kenji SekikawaAbstract:KK Mouse is known as a polygenic model for noninsulin-dependent diabetes mellitus with moderate obesity. To identify the quantitative trait loci (QTLs) responsible for the body weight in KK, linkage analysis with 97 microsatellite markers was carried out into 192 F2 progeny, comprising 93 mice with a/a genotype at agouti locus and 99 mice with A(y)/a genotype, of a cross between C57BL/6J female and KK-A(y) (A(y) congenic) male, thereby the influence of A(y) allele on the quantitative regulation of body weight was also examined. In F2 a/a mice, we identified a QTL on Chromosome (Chr) 4, and two loci with suggestive linkage on Chrs 15 and 18. In F2 A(y)/a mice, a QTL was identified on Chr 6, and two loci with suggestive linkage were identified on Chrs 4 and 16. That the QTL on Chr 4 was held in common between F2 a/a and F2 A(y)/a progenies implies that this locus may be a primary component regulating body weight in KK and KK-A(y). These results suggest that the body weight in KK is controlled by multiple genes, and the different combination of loci is involved in the presence of A(y) allele. The QTL on Chr 6 seemed to determine the body weight by controlling fat deposition, because the linkage was identified on body weight and adiposity, and is suggested to be a component involved in the metabolic pathway in obesity caused by the A(y) allele.
Kenji Sekikawa - One of the best experts on this subject based on the ideXlab platform.
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Genetic analysis of non-insulin-dependent diabetes mellitus in KK and KK-Ay mice
European journal of endocrinology, 1998Co-Authors: Jun-ichi Suto, Saori Matsuura, Kenkichi Imamura, Harumichi Yamanaka, Kenji SekikawaAbstract:The KK Mouse is considered suitable as a polygenic model for human non-insulin-dependent diabetes mellitus. To identify the quantitative trait loci (QTLs) responsible for hyperglycemia and impaired glucose tolerance in KK mice, linkage analysis using 97 microsatellite markers was carried out in a 192 F2 progeny, comprising 93 mice with the a/a genotype at the agouti locus (chromosome 2) and 99 mice with the Ay/a genotype, produced by a cross between a C57BL/6J female and a KK-Ay (Ay congenic) male. In F2 a/a progenies, we identified a QTL for fasting glucose levels on chromosome 6 (LOD score 6.0) and three loci with suggestive linkage on chromosomes 3, 5 and 14, but could not identify loci accounting for glucose tolerance and plasma insulin levels. In F2 Ay/a progenies, there were no loci with statistically significant linkage, but three suggestive loci were identified: a locus for fasting glucose on chromosome 9, and two loci for glucose tolerance on chromosomes 1 and 8. It would thus appear that. although the fasting glucose level is controlled by QTLs in KK mice, these QTLs may be masked by the strong hyperglycemic influence of the Ay allele. Suggestive loci accounting for glucose tolerance may interact with the Ay allele, since these loci were identified only in F2 Ay/a progeny. This is consistent with the finding that the impaired glucose tolerance in KK mice is moderate and becomes overt when associated with the Ay allele.
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Genetics of obesity in KK Mouse and effects of A(y) allele on quantitative regulation.
Mammalian genome : official journal of the International Mammalian Genome Society, 1998Co-Authors: Jun-ichi Suto, Saori Matsuura, Kenkichi Imamura, Harumichi Yamanaka, Kenji SekikawaAbstract:KK Mouse is known as a polygenic model for noninsulin-dependent diabetes mellitus with moderate obesity. To identify the quantitative trait loci (QTLs) responsible for the body weight in KK, linkage analysis with 97 microsatellite markers was carried out into 192 F2 progeny, comprising 93 mice with a/a genotype at agouti locus and 99 mice with A(y)/a genotype, of a cross between C57BL/6J female and KK-A(y) (A(y) congenic) male, thereby the influence of A(y) allele on the quantitative regulation of body weight was also examined. In F2 a/a mice, we identified a QTL on Chromosome (Chr) 4, and two loci with suggestive linkage on Chrs 15 and 18. In F2 A(y)/a mice, a QTL was identified on Chr 6, and two loci with suggestive linkage were identified on Chrs 4 and 16. That the QTL on Chr 4 was held in common between F2 a/a and F2 A(y)/a progenies implies that this locus may be a primary component regulating body weight in KK and KK-A(y). These results suggest that the body weight in KK is controlled by multiple genes, and the different combination of loci is involved in the presence of A(y) allele. The QTL on Chr 6 seemed to determine the body weight by controlling fat deposition, because the linkage was identified on body weight and adiposity, and is suggested to be a component involved in the metabolic pathway in obesity caused by the A(y) allele.
