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

热量限制会增加肝脏5‘AMP激酶(AMPK)的活性。和胰升糖素受体一样，AMPK也是 卡路里限制必不可少，可延长寿命和健康寿命。因为AMPK在胰升糖素的下游 受体信号转导可能是高血糖素受体激活的AMPK是热量限制所必需的 改善健康Span我们认为肝脏中的胰高血糖素受体信号随着两种热量的增加而增加 限制和肥胖，依赖于胰高血糖素受体刺激的AMPK活性来延缓衰老。建议数 这项研究将扩展我们从父母拨款中获得的结果，以评估在 胰高血糖素受体缺失小鼠通过诱导肝细胞表达一种固有活性的AMPK。

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.