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インスリン非依存性糖尿病(NIDDM)におけるShc蛋白異常の解析

非胰岛素依赖型糖尿病（NIDDM）Shc蛋白异常分析

基本信息

批准号：
09770776
负责人：
笹岡利安
金额：
$ 1.41万
依托单位：
Toyama Medical and Pharmaceutical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Encouragement of Young Scientists (A)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1998
项目状态：
已结题

项目摘要

高血糖状態では細胞内に取り込まれた過剰なブドウ糖がヘキソサミン経路によりグルコサミンに代謝され、グルコサミンがインスリン抵抗性を惹起する中心的な役割を担う。そこで、糖尿病状態が動脈硬化の進展に及ぼす細胞レベルでの検討として、培養血管平滑筋細胞(A10)でのPDGF刺激による細胞増殖作用をBromodeoxyuridine(BrdU)の取り込みにより測定した結果、グルコサミン培養下では高血糖培養下に比し高度に細胞増殖を促進し、グルコサミンがインスリン抵抗性の発現に加え、糖尿病による動脈硬化促進に重要な役割を担うことを明らかにした。その分子機構として、PDGF受容体以後のシグナル伝達において、Shcのチロシンリン酸化とShcのGrb2への結合に異常が生じている結果を得た。チアゾリジン誘導体がインスリン抵抗性を改善するのに加え、本研究によりトログリタゾンがグルコサミンにより惹起される、Shcを介したシグナル伝達異常と細胞増殖の亢進を改善することを明らかにした。その機序として血管平滑筋細胞では核内受容体PPARγの発現量は僅かであり、PPARγ結合活性の異なったチアゾリジン誘導体でも同様の効果を示したことから、チアゾリジン誘導体の動脈硬化抑制作用発現にはインスリン抵抗性の改善とは異なり、PPARγを介さずに作用すると考えられる新知見を得た。さらに、NIDDM患者でのShc遺伝子異常の有無に関する検討として、Shc遺伝子異常がNIDDMの発症と病態に関与する可能性を調べるため、NIDDM患者から得られたgenomic DNAのshc遺伝子をSSCPにより解析した結果、大血管合併症が高度に進行したNIDDM群でpolymorphysmsを認めるという興味深い結果を得たため、その遺伝子異常をシークエンシングにて確認中である。

Hyperglycemia is a condition of high blood sugar. The intracellular concentration of glucose, sugar, sugar, The results of Bromodeoxyuridine (BrdU) were measured by cell culture, hyperglycemia, hyperglycemia and hyperglycemia. This is an important step in the development of diabetes mellitus, diabetes, diabetes and diabetes. The molecular mechanism of Shc, the PDGF acceptor, and the Shc receptor were used to obtain the following results. The results showed that the drug was acidified and acidified, and the results were obtained in combination with the results of the laboratory test. In this study, we found that there was an increase in resistance. In this study, there was an increase in the level of resistance. In this study, the disease was induced, Shc was induced, and the colonization was increased. The sequence showed that the vascular smooth muscle cells had an inhibitory effect on the activity of PPAR gamma-ray receptor in the nucleus of vascular smooth tendon cells, and that the inhibitory effect of PPAR γ-ray on vascular smooth muscle cells showed that the vascular smooth muscle cells had an inhibitory effect on the resistance of vascular smooth muscle cells, and the effect of PPAR gamma-ray on vascular smooth muscle cells showed that it improved the resistance of vascular smooth muscle cells, and the effect of PPAR gamma-ray on vascular smooth muscle cells showed that it improved the resistance of vascular smooth muscle cells. Patients with NIDDM often have no symptoms of NIDDM symptoms, Shc patients often have symptoms of NIDDM symptoms, patients with NIDDM have genomic DNA symptoms, shc patients have SSCP symptoms, and patients with macrovascular disease have high levels of NIDDM. The results of the analysis of the results, the results of the analysis of the symptoms of the patients with macrovascular disease, the results of the analysis of the symptoms of the patients with macrovascular disease, the results of the analysis of the symptoms of the patients with macrovascular disease, the results of the analysis of the symptoms of the patients with macrovascular disease, the results of the analysis of the symptoms of the patients with macrovascular disease, the results of the analysis of the results showed that the symptoms of the patients with macrovascular disease were significantly higher than those of the control group. Please tell me that you are in the process of confirming that you are in the process of being confirmed.