AMPK plays a key role in maintaining cellular and whole body energy balance. It is found in all cells and tissues, but most importantly in skeletal muscle, liver, and adipose tissue. AMPK activation shifts both intracellular and whole body metabolism away from cholesterol, fatty acid and triglyceride synthesis (fat storage) and towards ß-oxidation (fat breakdown, energy production). Because exercise has similar metabolic effects in skeletal muscle to AMPK activation, AMPK has informally been referred to as "exercise in a bottle" or the "jogging pill." AMPK activity is also up-regulated by hormones secreted from the GI tract and from adipose tissue, including ghrelin, leptin, and adiponectin, and is inhibited by increases in amino acids, glucose, or insulin.
In Type 2 diabetes, a build-up of lipid within skeletal muscle suppresses the muscle cell's ability to take in glucose from the blood when stimulated to do so by insulin (termed insulin resistance), resulting in elevated blood glucose levels. The spillover of glucose is taken up by the liver for triglyceride synthesis, thereby contributing to the higher plasma triglycerides and lower HDL levels associated with insulin resistance. In addition the higher blood glucose levels evoke pancreatic beta cell insulin secretion that sustained over time contributes to the development of beta cell failure. A direct small molecule activator of AMPK that works independently of insulin levels has been shown in published reports to reduce insulin resistance in skeletal muscles of rat and mice models of Type 2 diabetes, along with reductions in blood glucose, serum triglycerides, and intramuscular fat stores, suggesting that activators of AMPK may be useful in the treatment of Type 2 diabetes.