The role of PI 3-kinase on insulin action and its alteration in diabetic condition
PI 3-激酶对胰岛素作用的作用及其在糖尿病状态下的改变
基本信息
- 批准号:09470214
- 负责人:
- 金额:$ 8.19万
- 依托单位:
- 依托单位国家:日本
- 项目类别:Grant-in-Aid for Scientific Research (B)
- 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
- 来源:
- 关键词:
项目摘要
Activation of p85/p110 type PI-kinase has been shown to be necessary for the insulin-induced glucose metabolism. Thus, we have investigated (1) The altered p85/p110 type PI-kinase activation in the insulin resistant condition, and (2) The alteration of the cellular content of phosphorylated phospholipid by p85/p110 type PI-kinase end its role on cellular activities.(1) The altered p85/p110 type PI-kinase activation in the insulin resistant condition obesity and high-fat diet are regarded as the most common causes of insulin resistance in Japanese population. We reported that obesity induced by overeating leads to the marked impairment of p85/p110 type PI-kinase activation in either liver, muscle or fat tissues. In contrast, high-fat diet feeding resulted in moderate impairment of p85/p110 type PI-kinase activation in muscle and fat tissues, however, interestingly, in the liver the activation was markedly enhanced. These results indicate that the mechanism of insulin resistance caused by high-fat diet is quite different from that by overeating.(2) The alteration of the cellular content of phosphorylated phospholipid by p85/p110 type PI-kinase. We observed activation of p85/p110 type PI-kinase resulted in the increased cellular content of not only PI3-P, PI3, 4-P2, PI3, 4, 5-P3 but also PI4-P and PI4, 5-P2 markedly. This suggests that p85/p110 type PI-kinase possesses a high PI 4-kinase activity. In addition, we observed the PI 4-kinase activity of p85/p110 type PI-kinase is involved in the actin rearrangement and the translocation of glucose transporter to the cell surface. These findings are surprising and can be a breakthrough to understand the molecular mechanism of insulin action and/or insulin resistance in NIDDM patients.
p85/p110型PI-激酶的激活已被证明是胰岛素诱导的葡萄糖代谢所必需的。因此,我们研究了(1)在胰岛素抵抗条件下改变的p85/p110型PI-激酶活化,和(2)由p85/p110型PI-激酶引起的细胞内磷酸化磷脂含量的改变及其对细胞活性的作用。(1)在胰岛素抵抗条件下,肥胖和高脂饮食中p85/p110型PI激酶活化的改变被认为是日本人群胰岛素抵抗的最常见原因。我们报道了暴饮暴食引起的肥胖导致肝脏、肌肉或脂肪组织中p85/p110型PI激酶活化的显著损害。相反,高脂饮食喂养导致肌肉和脂肪组织中p85/p110型PI-激酶活化的中度损伤,然而,有趣的是,在肝脏中的活化显著增强。提示高脂饮食引起胰岛素抵抗的机制与暴饮暴食有很大不同。(2)p85/p110型PI激酶对细胞内磷酸化磷脂含量的影响我们观察到p85/p110型PI-激酶的激活不仅使细胞内PI 3-P、PI 3,4-P2、PI 3,4,5-P3含量显著增加,而且使PI 4-P和PI 4,5-P2含量显著增加。这表明p85/p110型PI-激酶具有高PI 4-激酶活性。此外,我们观察到p85/p110型PI-激酶的PI 4-激酶活性参与肌动蛋白重排和葡萄糖转运蛋白向细胞表面的移位。这些发现是令人惊讶的,并且可能是理解NIDDM患者中胰岛素作用和/或胰岛素抵抗的分子机制的突破。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
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专利数量(0)
Terasaki,J.et al.: "Role of JTT-501,a new insulin sensitizer,in restoring impaird steps in the pathwya of rats fed a-high fat diet" Diabetologia. 41. 400-409 (1998)
Terasaki, J. 等人:“JTT-501(一种新型胰岛素增敏剂)在恢复高脂肪饮食大鼠通路中受损步骤中的作用”糖尿病学。
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Anai,N.,et al.: "Affered expression levels and impaired steps in the pathway to phosphafidy*inosito* 3-kinase activation vic IRS-1 and 2 in Zucker fctty rats"Diabetes. 47. 13-23 (1998)
Anai,N.,et al.:“Zucker fctty 大鼠中 IRS-1 和 2 的磷脂酰肌醇 3-激酶激活途径中的表达水平和受损步骤”糖尿病。
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Anai,M et al.: "Altered expression levels and impaired steps in the pathway to phosphatidylinesitol 3-kinase activation via insulin receptor substrates 1 and 2 in Zuker fatty rats" Diabetes. 47. 13-23 (1998)
Anai,M 等人:“Zuker 脂肪大鼠中通过胰岛素受体底物 1 和 2 改变了磷脂酰醇 3-激酶激活途径中的表达水平和受损步骤”糖尿病。
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Isihhara,H.,et al.: "Enhanced phosphoinositide hydrolysis via overexpressions phaspholipase C β1 or δ1 inhibits stimulus-induced insulin release in insulinoma MIN6 cells"Biochem.Biophys.Res.Commun.. 254. 77-82 (1999)
Isihhara, H. 等人:“通过过表达磷脂酶 C β1 或 δ1 增强磷酸肌醇水解抑制胰岛素瘤 MIN6 细胞中刺激诱导的胰岛素释放”Biochem.Biophys.Res.Commun. 254. 77-82 (1999)
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Anai, N., Funaki, M., Ogihara, T., Kanda, A., Onishi, Y., Sakoda, H., Inukai, K., Nawano, M., Fukushima, Y., Yazaki, Y., Kikuchu, M., Oka, Y., Asano, T.: "Enhanced insulin-stimulated activation of PI 3-kinase in the liver of high-fat fed rats."Diabetes. 4
Anai, N.、Funaki, M.、Ogihara, T.、Kanda, A.、Onishi, Y.、Sakoda, H.、Inukai, K.、Nawano, M.、Fukushima, Y.、Yazaki, Y.、
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ASANO Tomoichiro其他文献
ASANO Tomoichiro的其他文献
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{{ truncateString('ASANO Tomoichiro', 18)}}的其他基金
Role of INTS6 in the adipose differentiation
INTS6 在脂肪分化中的作用
- 批准号:
24659445 - 财政年份:2012
- 资助金额:
$ 8.19万 - 项目类别:
Grant-in-Aid for Challenging Exploratory Research
Elucidation of molecular mechanism underlying insulin resistane and inflammation
阐明胰岛素抵抗和炎症的分子机制
- 批准号:
23390242 - 财政年份:2011
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$ 8.19万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Elucidation of the role of Pin1 on the adipose differentiation
阐明 Pin1 对脂肪分化的作用
- 批准号:
22659175 - 财政年份:2010
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$ 8.19万 - 项目类别:
Grant-in-Aid for Challenging Exploratory Research
Elucidation of the molecular mechanisms underlying insulin resistance and metabolic disorders using a proteomics technology
使用蛋白质组学技术阐明胰岛素抵抗和代谢紊乱的分子机制
- 批准号:
20390258 - 财政年份:2008
- 资助金额:
$ 8.19万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Elucidation of the molecular mechanisms underlying metabolic disorders using protemomics analysis
使用蛋白质组学分析阐明代谢紊乱的分子机制
- 批准号:
18390271 - 财政年份:2006
- 资助金额:
$ 8.19万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Elucidation of the molecular mechanisms underlying insulin and exercise-induced effects on metabolism and vascular cells
阐明胰岛素和运动对代谢和血管细胞影响的分子机制
- 批准号:
16390262 - 财政年份:2004
- 资助金额:
$ 8.19万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Molecular mechanisms of insulin-and exercise-induced glucose uptake
胰岛素和运动诱导的葡萄糖摄取的分子机制
- 批准号:
14370334 - 财政年份:2002
- 资助金额:
$ 8.19万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Molecular mechanism underlying the GLUT4 translocation and its abnormality in diabetes mellitus
糖尿病GLUT4易位及其异常的分子机制
- 批准号:
12470224 - 财政年份:2000
- 资助金额:
$ 8.19万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
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