AMP-activated protein kinase (AMPK) is a heterotrimeric complex that acts as sensor of cellular energy levels. The signaling cascades initiated by activating AMPK are critical to regulating metabolic events in the liver, skeletal muscle, heart, adipose tissue, and pancreas. An impairment in fuel metabolism that occurs in obesity is a factor leading to type 2 diabetes. The insulin resistance associated with type 2 diabetes is most profound at the level of skeletal muscle, the primary site of glucose and fatty acid utilization. Activation of AMPK is of interest for the treatment of type 2 diabetes.