The Experts below are selected from a list of 1164 Experts worldwide ranked by ideXlab platform
Jun Zha - One of the best experts on this subject based on the ideXlab platform.
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interleukin 1β targeted vaccine improves glucose control and β cell function in a diabetic kk ay Mouse model
PLOS ONE, 2016Co-Authors: Jun Zha, Xiaowei Chi, Xiangmeng Liu, Dongqun Liu, Jie Zhu, Ruitian LiuAbstract:Interleukin-1β (IL-1β) has been implicated as a key proinflammatory cytokine involved in the pancreatic islet inflammation of type 2 diabetes mellitus (T2DM). Excess IL-1β impairs islet function by inducing insulin resistance and β-cell apoptosis. Therefore, specifically reducing IL-1β activity provides a therapeutic improvement for T2DM by sustaining the inhibition of IL-1β-mediated islet inflammation. In this study, we developed an IL-1β-targeted epitope peptide vaccine adjuvanted with polylactic acid microparticles (1βEPP) and applied it to a diabetic KK-Ay Mouse model. Results showed that the 1βEPP elicited high antibody responses, which neutralized the biological activity of IL-1β, and induced barely detectable inflammatory activity. 1βEPP immunization reduced body weight gain, protected KK-Ay mice from hyperglycemia, improved glucose tolerance and insulin sensitivity, and decreased the serum levels of free fatty acids, total cholesterol and triglyceride. Moreover, 1βEPP restored β-cell mass; inhibited β-cell apoptosis; decreased the expression of IL-1β; and interrupted NF-κB activation by reducing IKKβ and pRelA levels. These studies indicated that the IL-1β-targeted vaccine may be a promising immunotherapeutic for T2DM treatment.
Rie Temaru - One of the best experts on this subject based on the ideXlab platform.
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effect of glimepiride hoe 490 on insulin receptors of skeletal muscles from genetically diabetic kk ay Mouse
European Journal of Pharmacology, 1996Co-Authors: Yoshihisa Takada, Yasumitsu Takata, Masanori Iwanishi, Takeshi Imamura, Tasuku Sawa, Hisao Morioka, Hajime Ishihara, Manabu Ishiki, Isao Usui, Rie TemaruAbstract:Abstract A new sulfonylurea, glimepiride (HOE 490), has been developed for the glycemic control in non-insulin-dependent diabetes mellitus. We examined the effect of glimepiride on glucose and insulin levels in KK-Ay mice, an animal model of non-insulin-dependent diabetes mellitus, which is characterized by hyperglycemia and hyperinsulinemia. Administration of glimepiride (0.5 mg/kg/day) for 8 weeks to KK-Ay mice resulted in decrease in glucose (297 ± 36 to 250 ± 51 mg/dl) and insulin (76 ± 14 to 41 ± 14 μU/ml) levels. To clarify the mechanism of the agent, we examined the effect of this new drug on insulin receptors in the skeletal muscles. There was no difference in insulin binding to the receptors from both glimepiride-treated and -untreated KK-Ay mice muscles. The insulin-stimulated autophosphorylation of insulin receptors from KK-Ay mice was decreased compared to that from normal mice (5 ± 1 vs. 39 ± 13% over basal). Glimepiride did not ameliorate impaired insulin-stimulated insulin receptor autophosphorylation. To determine the effect of glimepiride on post-insulin receptor signaling pathway, we measured 2-[3H]glycerol incorporation into diacylglycerol in the cultured rat fibroblast cell line overexpressing human insulin receptors. Glimepiride (100 μM) as well as insulin (10 nM) significantly stimulated diacylglycerol production. These results suggest that glimepiride has a potent extrapancreatic effect on glucose metabolism and may directly stimulate glucose transport activity through phospholipid signaling pathway, but not through insulin receptor kinase signaling pathway.
Ruitian Liu - One of the best experts on this subject based on the ideXlab platform.
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interleukin 1β targeted vaccine improves glucose control and β cell function in a diabetic kk ay Mouse model
PLOS ONE, 2016Co-Authors: Jun Zha, Xiaowei Chi, Xiangmeng Liu, Dongqun Liu, Jie Zhu, Ruitian LiuAbstract:Interleukin-1β (IL-1β) has been implicated as a key proinflammatory cytokine involved in the pancreatic islet inflammation of type 2 diabetes mellitus (T2DM). Excess IL-1β impairs islet function by inducing insulin resistance and β-cell apoptosis. Therefore, specifically reducing IL-1β activity provides a therapeutic improvement for T2DM by sustaining the inhibition of IL-1β-mediated islet inflammation. In this study, we developed an IL-1β-targeted epitope peptide vaccine adjuvanted with polylactic acid microparticles (1βEPP) and applied it to a diabetic KK-Ay Mouse model. Results showed that the 1βEPP elicited high antibody responses, which neutralized the biological activity of IL-1β, and induced barely detectable inflammatory activity. 1βEPP immunization reduced body weight gain, protected KK-Ay mice from hyperglycemia, improved glucose tolerance and insulin sensitivity, and decreased the serum levels of free fatty acids, total cholesterol and triglyceride. Moreover, 1βEPP restored β-cell mass; inhibited β-cell apoptosis; decreased the expression of IL-1β; and interrupted NF-κB activation by reducing IKKβ and pRelA levels. These studies indicated that the IL-1β-targeted vaccine may be a promising immunotherapeutic for T2DM treatment.
Xiangmeng Liu - One of the best experts on this subject based on the ideXlab platform.
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interleukin 1β targeted vaccine improves glucose control and β cell function in a diabetic kk ay Mouse model
PLOS ONE, 2016Co-Authors: Jun Zha, Xiaowei Chi, Xiangmeng Liu, Dongqun Liu, Jie Zhu, Ruitian LiuAbstract:Interleukin-1β (IL-1β) has been implicated as a key proinflammatory cytokine involved in the pancreatic islet inflammation of type 2 diabetes mellitus (T2DM). Excess IL-1β impairs islet function by inducing insulin resistance and β-cell apoptosis. Therefore, specifically reducing IL-1β activity provides a therapeutic improvement for T2DM by sustaining the inhibition of IL-1β-mediated islet inflammation. In this study, we developed an IL-1β-targeted epitope peptide vaccine adjuvanted with polylactic acid microparticles (1βEPP) and applied it to a diabetic KK-Ay Mouse model. Results showed that the 1βEPP elicited high antibody responses, which neutralized the biological activity of IL-1β, and induced barely detectable inflammatory activity. 1βEPP immunization reduced body weight gain, protected KK-Ay mice from hyperglycemia, improved glucose tolerance and insulin sensitivity, and decreased the serum levels of free fatty acids, total cholesterol and triglyceride. Moreover, 1βEPP restored β-cell mass; inhibited β-cell apoptosis; decreased the expression of IL-1β; and interrupted NF-κB activation by reducing IKKβ and pRelA levels. These studies indicated that the IL-1β-targeted vaccine may be a promising immunotherapeutic for T2DM treatment.
Yasushi Kaburagi - One of the best experts on this subject based on the ideXlab platform.
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differential proteome analysis of serum proteins associated with the development of type 2 diabetes mellitus in the kk ay Mouse model using the itraq technique
Journal of Proteomics, 2013Co-Authors: Eri Takahashi, Akinori Okumura, Hiroyuki Unokikubota, Hisashi Hirano, Masato Kasuga, Yasushi KaburagiAbstract:Abstract To identify candidate serum molecules associated with the progression of type 2 diabetes mellitus (T2DM), we carried out differential proteomic analysis using the KK-Ay Mouse, an animal model of T2DM with obesity. We employed an iTRAQ-based quantitative proteomic approach to analyze the proteomic changes in the sera collected from a pair of 4-week-old KK-Ay versus C57BL/6 mice. Among the 227 proteins identified, a total of 45 proteins were differentially expressed in KK-Ay versus C57BL/6 mice. We comparatively analyzed a series of the sera collected at 4 and 12 weeks of age from KK-Ay and C57BL/6 mice for the target protein using multiple reaction monitoring analysis, and identified 8 differentially expressed proteins between the sera of these mice at both time points. Among them, serine (or cysteine) peptidase inhibitor, clade A, member 3K (SERPINA3K) levels were elevated significantly in the sera of KK-Ay mice compared to C57BL/6 mice. An in vitro assay revealed that the human homologue SERPINA3 increased the transendothelial permeability of retinal microvascular endothelial cells, which may be involved in the pathogenesis of diabetes and/or diabetic retinopathy. With the identified proteins, our proteomics study could provide valuable clues for a better understanding of the underlying mechanisms associated with T2DM. Biological significance In this paper, we investigated the serum proteome of KK-Ay mice in a pre-diabetic state compared to that of wild type controls in an attempt to uncover early diagnostic markers of diabetes that are maintained through a diabetic phenotype. We used iTRAQ-based two-dimensional LC–MS/MS serum profiling, and identified several differentially expressed proteins at the pre-diabetic stage. The differential expression was confirmed by multiple reaction monitoring assay, which is fast gaining ground as a sensitive, specific, and cost-effective methodology for relative quantification of the candidate proteins. Using these techniques, we have identified eight candidate proteins of interest including SERPINA3K, which may be important in the pathology of T2DM and/or diabetic retinopathy.
