Central and peripheral actions of insulin for the control of muscle capillary recruitment

胰岛素控制肌肉毛细血管募集的中枢和外周作用

• 批准号: nhmrc : 457603
• 负责人: Dr Derek Choi-Lundberg
• 金额: $ 28.94万
• 依托单位: Menzies Institute for Medical Research
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2007
• 资助国家: 澳大利亚
• 起止时间: 2007-01-01 至 2009-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/central-peripheral-actions-capillary-recruitment/95918
• 关键词: Central; peripheral; actions; insulin; control

Type 2 diabetes is on the increase world wide and reflects the ever-increasing incidence of obesity. Whereas the likely cause of type 2 diabetes includes low physical activity and high fat diet, the primary metabolic abnormality is likely to be muscle insulin resistance. The cause of this resistance is controversial, but may stem from microvascular dysfunction where muscle becomes poorly perfused and unresponsive to the action of insulin to recruit capillary flow. In this project we will further extend our seminal discoveries that insulin mediates capillary recruitment under normal circumstances and that in various models of insulin resistance insulin's ability to increase the perfusion of muscle is markedly impaired. We will explore the hypothesis, that insulin controls microvascular perfusion of muscle by a central neural mechanism ending at terminal arterioles on the vasculature and endeavour to identify the details of this control. We will use in-house novel techniques for examining both the role of central control mechanisms involving the brain as well as peripheral mechanisms by local infusion of various agents likely to either enhance or block insulin's microvascular action. A positive outcome will enhance our understanding of insulin action and the insulin resistance that precedes type 2 diabetes. There is also the possible outcome that important clues will be obtained leading to new therapeutic agents that could be used to treat type 2 diabetes.

2型糖尿病在世界范围内呈上升趋势，反映了肥胖症发病率的不断增加。2型糖尿病的可能病因包括低体力活动和高脂肪饮食，而主要的代谢异常可能是肌肉胰岛素抵抗。这种抵抗的原因是有争议的，但可能源于微血管功能障碍，肌肉变得灌注不良，对胰岛素募集毛细血管流动的作用没有反应。在这个项目中，我们将进一步扩展我们的开创性发现，即胰岛素在正常情况下介导毛细血管募集，在各种胰岛素抵抗模型中，胰岛素增加肌肉灌注的能力明显受损。我们将探讨假设，胰岛素控制肌肉微血管灌注的中枢神经机制结束于末梢小动脉在脉管系统和努力确定这种控制的细节。我们将使用内部的新技术，通过局部输注各种可能增强或阻断胰岛素微血管作用的药物，来检查涉及大脑的中枢控制机制和外周机制的作用。一个积极的结果将增强我们对胰岛素作用和胰岛素抵抗在2型糖尿病之前的理解。还有一个可能的结果是，将获得重要的线索，导致新的治疗药物，可用于治疗2型糖尿病。