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肥満2型糖尿病モデルSDT fattyラットにおけるメトホルミンの作用解析および血行動態の病態解析
http://hdl.handle.net/10191/00051786
http://hdl.handle.net/10191/000517868b064677-a0b5-42e2-afd6-b211c91dc069
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Item type | 学位論文 / Thesis or Dissertation(1) | |||||
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公開日 | 2020-08-31 | |||||
タイトル | ||||||
タイトル | 肥満2型糖尿病モデルSDT fattyラットにおけるメトホルミンの作用解析および血行動態の病態解析 | |||||
言語 | ||||||
言語 | jpn | |||||
資源タイプ | ||||||
資源 | http://purl.org/coar/resource_type/c_46ec | |||||
タイプ | thesis | |||||
著者 |
村井, 康高
× 村井, 康高 |
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抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | The number of diabetic patients has recently been increasing worldwide, and numerous anti-diabetic drugs have been developed to control blood glucose level. In particular, metformin, which exhibits glucose-lowering effects by suppressing gluconeogenesis in the liver, is widely used as a first-line oral anti-diabetic drug for type 2 diabetes. Diabetes is associated with pathogenesis of other diseases and is known as one of the risk factor of peripheral artery disease (PAD). PAD is defined as peripheral blood flow impairment, especially in legs, caused by atherosclerotic stenosis. The disease decreases the quality of life (QOL) due to intermittent claudication or necrosis in the leg. In the first part of this study, the pharmacological effects of metformin were investigated using female and male Spontaneously Diabetic Torii (SDT) fatty rats, a new obese type 2 diabetic model. Two experiments were performed: an assessment of repeated treatment with metformin in female SDT fatty rats from 5 to 10 weeks of age, and an assessment of repeated treatment with metformin in male SDT fatty rats from 6 to 10 weeks of age. In female SDT fatty rats, metformin treatment achieved good glycemic control and prevented the development of sensory nerve dysfunction. In male SDT fatty rats, metformin also decreased blood glucose levels 4 weeks after treatment. In non-clinical research regarding PAD, a hindlimb ischemic model induced by femoral artery ligation is often used as a PAD model. In this model, non-metabolic syndrome animals are mainly used. However, many PAD patients have metabolic syndrome components such as hypertension, diabetes, and dyslipidemia in their background, and show endothelial dysfunction. Therefore, it is very important to establish a PAD model based on animals with metabolic syndrome. In the second part of this study, the usefulness of SDT fatty rats as a new PAD animal model was investigated. It is revealed that the hindlimb blood flow in SDT fatty rats was significantly lower than that in Sprague-Dawley (SD) rats under non-ischemic conditions. Furthermore, SDT fatty rats showed significantly higher plasma nitrogen oxide (NOx) level, shorter prothrombin time (PT), and shorter activated partial thromboplastin time (APTT) than SD rats. In the third part of this study, the hindlimb blood flow in SDT fatty rats after femoral artery ligation was evaluated. The change in blood flow at 7 days after induction of hindlimb ischemia was significantly decreased, and the number of Von Willebrand Factor (VWF)-positive vessels in gastrocnemius muscles was significantly decreased in the ligated SDT fatty rats. Results from the second and the third experiments suggest that the excess production of reactive oxygen species (ROS) and activation of coagulation could be involved in the lower blood flow in non-ischemic rats, and decreased angiogenesis could be involved in the poor recovery of blood flow in SDT fatty rats with hindlimb ischemia. Taken together, SDT fatty rats might be useful for the development of novel anti-diabetic agents that show potential to improve glucose metabolic disorders in the liver, and also useful as a new PAD model with metabolic syndrome. | |||||
書誌情報 | p. 1-70 | |||||
著者版フラグ | ||||||
値 | ETD | |||||
学位名 | ||||||
学位名 | 博士(農学) | |||||
学位授与機関 | ||||||
学位授与機関名 | 新潟大学 | |||||
学位授与年月日 | ||||||
学位授与年月日 | 2020-03-23 | |||||
学位授与番号 | ||||||
学位授与番号 | 13101甲第4775号 | |||||
学位記番号 | ||||||
内容記述タイプ | Other | |||||
内容記述 | 新大院博(農)甲第206号 |