Comparison between AICAR and exercise-induced stimulation of skeletal muscle AMP-K on fat/glucose metabolism in diabetes

AICAR 与运动诱导的骨骼肌 AMP-K 刺激对糖尿病患者脂肪/葡萄糖代谢的比较

• 批准号: nhmrc : 156703
• 负责人: A/Pr Glenn Ward
• 金额: $ 23.14万
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2001
• 资助国家: 澳大利亚
• 起止时间: 2001-01-01 至 2003-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/comparison-aicar-exercise-metabolism-diabetes/95139
• 关键词: Comparison; between; AICAR; exercise; induced

Background and Rationale: Exercise is important in the life of the diabetic. In well controlled diabetes, the rates of whole body sugar usage and energy production in skeletal muscle (SkM) in response to acute exercise are similar to non-diabetics. However in diabetics, little information is available as to how SkM processes sugar and produces energy during exercise. Insulin controls SkM sugar and energy processing in sedentary subjects. During exercise, these processes are controlled by non-insulin factors. The chemical catalyst AMP activated protein kinase (AMP-K), which has been investigated only in normal exercising rats, is an important alternative regulator of acute sugar processing and energy supply for exercising SkM. No studies of AMP-K activity are available in diabetes. Our studies will focus on i) how important is the stimulation of SkM AMP-K in diabetes to efficient SkM sugar processing and energy production; ii) if the benefits of exercise can be simulated by pharmacological stimulation of AMP-K in sedentary diabetic subjects. We aim to i) compare the metabolic effects of exercise vs pharmacological stimulation of AMP-K in normal and diabetic subjects; ii) define the molecular mechanisms which trigger the AMP-K metabolic responses; iii) determine if the circulating levels of insulin, blood sugar and-or blood fat influence the AMP-K metabolic responses. Likely Outcomes: pharmacological stimulation of AMP-K will improve SkM sugar metabolism, but less so in diabetes. The associated AMP-K stimulation of SkM fat metabolism may blunt the beneficial SkM sugar responses, particularly in diabetes. This information will be used in future drug developments for diabetics which aim to simulate the beneficial AMP-K metabolic effects of exercise.

背景和原理：运动在糖尿病患者的生活中很重要。在控制良好的糖尿病患者中，全身糖的使用率和骨骼肌（SkM）对急性运动的能量产生率与非糖尿病患者相似。然而，在糖尿病患者中，关于SkM如何在运动过程中处理糖和产生能量的信息很少。胰岛素控制久坐受试者的SkM糖和能量加工。在运动过程中，这些过程由非胰岛素因素控制。化学催化剂AMP激活的蛋白激酶（AMP-K）是一种重要的替代性调节剂，调节急性糖加工和运动时SkM的能量供应，目前仅在正常运动大鼠中进行了研究。没有关于AMP-K活性在糖尿病中的研究。我们的研究将集中在i）糖尿病中刺激SkM AMP-K对有效SkM糖加工和能量产生的重要性; ii）运动的益处是否可以通过药理学刺激久坐的糖尿病受试者中的AMP-K来模拟。我们的目的是i）比较运动与药物刺激对正常和糖尿病受试者中AMP-K的代谢作用; ii）定义触发AMP-K代谢反应的分子机制; iii）确定胰岛素、血糖和/或血脂的循环水平是否影响AMP-K代谢反应。可能的结果：药理学刺激AMP-K将改善SkM糖代谢，但在糖尿病中效果较差。相关的AMP-K刺激SkM脂肪代谢可能会减弱有益的SkM糖反应，特别是在糖尿病中。这些信息将用于未来的糖尿病药物开发，旨在模拟运动对AMP-K代谢的有益影响。