Investigation of the Roles of Protein Kinase C epsilon in Insulin Secretion and Insulin Clearance

蛋白激酶 C ε 在胰岛素分泌和胰岛素清除中的作用研究

• 批准号: nhmrc : 376022
• 负责人: A/Pr Carsten Schmitz-Peiffer
• 金额: $ 41.82万
• 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: 2006
• 资助国家: 澳大利亚
• 起止时间: 2006-01-01 至 2008-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/investigation-roles-protein-insulin-clearance/101377
• 关键词: Investigation; Roles; Protein; Kinase; epsilon

The rise in blood insulin levels after a meal normally reduces blood sugar levels by increasing glucose uptake and storage in certain tissues, especially muscle. Type 2 diabetes is characterized in part by a failure of the pancreas to produce adequate insulin in response to increases in blood sugar. This loss of insulin secretion has been strongly linked to increases in the availability of fat, although the reasons for this are not clear. We have recently found that mice lacking a specific enzyme (protein kinase C epsilon) are much less susceptible to the problems in dealing with blood sugar that are caused by a high fat diet. We showed that this is due partly to improved insulin secretion, and also to a slower breakdown of insulin by the liver, which increases its availability to target tissues. The aim of this project is to investigate the mechanisms occurring in the liver and in the pancreas by which this enzyme contributes to improved insulin action. Firstly, we will examine insulin uptake in liver cells, to investigate how the enzyme controls this process. Secondly, we will determine the mechanism through which the activation of the enzyme, upon increased fat supply to pancreatic beta-cells, reduces insulin secretion in response to glucose. Finally, will assess the relative importance of these two actions of the enzyme in improving the control of blood sugar levels. This work will lead to a better understanding of the mechanisms by which fat oversupply, and hence obesity, can play a role in the development of Type 2 diabetes, 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.

餐后血液胰岛素水平的升高通常通过增加葡萄糖的摄取和某些组织（特别是肌肉）中的储存来降低血糖水平。2型糖尿病的部分特征是胰腺不能产生足够的胰岛素来响应血糖的增加。这种胰岛素分泌的减少与脂肪可用性的增加密切相关，尽管其原因尚不清楚。我们最近发现，缺乏特定酶（蛋白激酶C β）的小鼠对高脂肪饮食引起的血糖处理问题的敏感性要小得多。我们发现，这部分是由于改善了胰岛素分泌，也是由于肝脏对胰岛素的分解较慢，这增加了其对靶组织的可用性。该项目的目的是研究这种酶有助于改善胰岛素作用的肝脏和胰腺中发生的机制。首先，我们将检查肝细胞中的胰岛素摄取，以研究酶如何控制这一过程。其次，我们将确定在增加胰腺β细胞的脂肪供应时，酶的激活减少胰岛素分泌对葡萄糖的反应的机制。最后，将评估这两种酶在改善血糖水平控制方面的相对重要性。这项工作将导致更好地了解脂肪供应过剩和肥胖在2型糖尿病发展中发挥作用的机制，以便它们可以成为开发新的和更有效的治疗疾病和预防其发作的目标。