Investigations to Assess the Role of Glucagon Signaling in Healthspan and Aging

热量限制增加肝脏5 'AMP激酶（AMPK）活性。与胰高血糖素受体一样，AMPK是 对限制卡路里以延长寿命和健康至关重要。因为AMPK是胰高血糖素的下游 受体信号传导，胰高血糖素受体激活的AMPK可能是热量限制所必需的， 改善健康寿命我们提出肝脏胰高血糖素受体信号传导，其随着卡路里和胰岛素的增加而增加。 限制和肥胖，依赖于胰高血糖素受体刺激的AMPK活性减缓衰老。拟议 这项研究将扩展我们的研究结果，从父母补助金，以评估能力，挽救受损的健康跨度， 胰高血糖素受体缺失小鼠通过诱导组成型活性AMPK的肝细胞表达。

Calorie restriction increases liver 5’AMP kinase (AMPK) activity. Like the glucagon receptor, AMPK is essential for calorie restriction to extend lifespan and healthspan. Because AMPK is downstream of glucagon receptor signaling it is possible that glucagon receptor activated AMPK is necessary for calorie restriction to improve healthspan We propose that glucagon receptor signaling at the liver, which increases with both calorie restriction and obesity, slows aging dependent upon glucagon receptor stimulated AMPK activity. The proposed study will extend our findings from the parent grant to assess the ability to rescue the impaired healthspan in glucagon receptor null mice by inducing hepatocyte expression of a constitutively active AMPK.