The Role of Protein Kinase C epsilon in the Generation of Lipid-Induced Insulin Resistance in Skeletal Muscle

蛋白激酶 C ε 在骨骼肌脂质诱导胰岛素抵抗产生中的作用

• 批准号: nhmrc : 230822
• 负责人: A/Pr Carsten Schmitz-Peiffer
• 金额: $ 31.66万
• 依托单位: Garvan Institute of Medical Research
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2003
• 资助国家: 澳大利亚
• 起止时间: 2003-01-01 至 2005-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/role-protein-kinase-skeletal-muscle/95789
• 关键词: Role; Protein; Kinase; epsilon; Generation

Insulin normally reduces blood sugar levels by increasing glucose uptake and storage in certain tissues, especially muscle. Type 2 diabetes is characterized by a failure of these tissues to respond adequately to insulin. This loss of sensitivity to the hormone is known as insulin resistance, and has been strongly linked to increases in the availability of fat, although the reasons for this are not clear. Certain fat molecules are able to cause the activation of pathways within cells which can interfere with the normal signalling of insulin. We have recently found that mice lacking an enzyme thought to be involved in such negative pathways are less susceptible to insulin resistance caused by high-fat feeding. The aim of this project is to investigate the mechanism by which this enzyme contributes to inhibition of insulin action. We will determine the step in normal insulin signalling which is blocked by the activation of the enzyme upon increased fat supply. This will help us to determine the pathway leading from the enzyme to insulin signalling. We will also identify the particular form of fat which leads to activation of the enzyme. This work will lead to a better understanding of the mechanisms by which fats can play a role in the generation of insulin resistance, so that they can be targeted both for the development of new and more effective treatments for the disorder and for prevention of its onset.

胰岛素通常通过增加某些组织（尤其是肌肉）中葡萄糖的摄取和储存来降低血糖水平。2型糖尿病的特征是这些组织对胰岛素的反应不足。这种对激素敏感性的丧失被称为胰岛素抵抗，并且与脂肪可用性的增加密切相关，尽管其原因尚不清楚。某些脂肪分子能够引起细胞内通路的激活，从而干扰胰岛素的正常信号传导。我们最近发现，缺乏一种被认为参与这种负向途径的酶的小鼠对高脂肪喂养引起的胰岛素抵抗不太敏感。本项目的目的是研究这种酶抑制胰岛素作用的机制。我们将确定正常胰岛素信号传导的步骤，该步骤在脂肪供应增加时被酶的激活所阻断。这将帮助我们确定从酶到胰岛素信号传导的途径。我们还将确定导致酶激活的脂肪的特定形式。这项工作将导致更好地了解脂肪在胰岛素抵抗产生中发挥作用的机制，以便它们可以成为开发新的和更有效的疾病治疗方法和预防其发作的目标。