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The Role of PTEN in Pancreatic Beta Cells and Insulin Promoter-expressing Neurons in Modulating Glucose Metabolism and Energy HomeostasisWang, Linyuan 06 December 2012 (has links)
PI3K signaling in pancreatic β cells has been shown to be important in modulating β cell mass and function under basal condition. Evidence suggests that a specific group of insulin promoter-expressing neurons also modulates glucose metabolism and energy homeostasis through their PI3K signaling. Thus we hypothesize that PI3K activation via PTEN deletion under the control of rat insulin promoter (RIP) in pancreatic β cells and RIP-expressing neurons will protect against hyperglycemia and diabetes in experimentally induced mouse models of type 2 diabetes. In Chapter IV, we showed that RIP-mediated PTEN deletion in pancreatic β cells led to PI3K activation and subsequent increased β cell mass and function, thus protected the mice from high fat diet (HFD)-induced diabetes. Furthermore in the absence of global leptin signaling, β cell-specific PTEN deletion maintained β cell function in the setting of severe insulin resistance, therefore prevented diabetes development. Interestingly, RIP-mediated PTEN deletion also resulted in increased peripheral insulin sensitivity due to PI3K activation in central nervous system. In Chapter V, we showed this increased insulin sensitivity was maintained after HFD feeding, which also contributed to the protection against diabetes. These mice also showed increased visceral adipogenesis and subcutaneous adiposity on HFD, which were dramatically attenuated in the absence of leptin signaling, indicated the essential role of peripheral leptin action in mediating the insulin sensitive phenotype from neuronal RIP PTEN deletion. Finally, we demonstrated that the insulin sensitizing phenotype in these mice was not mediated through ventromedial hypothalamic nuclei (VMH), such that VMH-specific PTEN deletion did not alter energy homeostasis or glucose metabolism. Together, the data from this thesis points to an inhibitory role of PTEN in both central nervous system and pancreatic β cells in glycemic control. Therefore, PTEN may represent a potential target for diabetes prevention and treatment.
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The Role of PTEN in Pancreatic Beta Cells and Insulin Promoter-expressing Neurons in Modulating Glucose Metabolism and Energy HomeostasisWang, Linyuan 06 December 2012 (has links)
PI3K signaling in pancreatic β cells has been shown to be important in modulating β cell mass and function under basal condition. Evidence suggests that a specific group of insulin promoter-expressing neurons also modulates glucose metabolism and energy homeostasis through their PI3K signaling. Thus we hypothesize that PI3K activation via PTEN deletion under the control of rat insulin promoter (RIP) in pancreatic β cells and RIP-expressing neurons will protect against hyperglycemia and diabetes in experimentally induced mouse models of type 2 diabetes. In Chapter IV, we showed that RIP-mediated PTEN deletion in pancreatic β cells led to PI3K activation and subsequent increased β cell mass and function, thus protected the mice from high fat diet (HFD)-induced diabetes. Furthermore in the absence of global leptin signaling, β cell-specific PTEN deletion maintained β cell function in the setting of severe insulin resistance, therefore prevented diabetes development. Interestingly, RIP-mediated PTEN deletion also resulted in increased peripheral insulin sensitivity due to PI3K activation in central nervous system. In Chapter V, we showed this increased insulin sensitivity was maintained after HFD feeding, which also contributed to the protection against diabetes. These mice also showed increased visceral adipogenesis and subcutaneous adiposity on HFD, which were dramatically attenuated in the absence of leptin signaling, indicated the essential role of peripheral leptin action in mediating the insulin sensitive phenotype from neuronal RIP PTEN deletion. Finally, we demonstrated that the insulin sensitizing phenotype in these mice was not mediated through ventromedial hypothalamic nuclei (VMH), such that VMH-specific PTEN deletion did not alter energy homeostasis or glucose metabolism. Together, the data from this thesis points to an inhibitory role of PTEN in both central nervous system and pancreatic β cells in glycemic control. Therefore, PTEN may represent a potential target for diabetes prevention and treatment.
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Establishment of non-invasive quantification of pancreatic beta cell mass in mice using SPECT/CT imaging with ¹¹¹In-labeled exendin-4 and its application to evaluation of diabetes treatment effects on pancreatic beta cell mass / ¹¹¹In標識exendin-4を用いたSPECT/CTによるマウス膵β細胞量の非侵襲的定量法の確立と、膵β細胞量に対する糖尿病治療効果の評価への応用Hamamatsu, Keita 23 March 2020 (has links)
京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第22363号 / 医博第4604号 / 新制||医||1043(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 川口 義弥, 教授 富樫 かおり, 教授 上本 伸二 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM
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