AMPK’s role in metabolism and its activation through exercise have been understood for some time. However, the possibility that AMPK could be activated pharmaceutically took longer to discover.

A key finding was the discovery that the tumor suppressor LKB1 is a direct upstream activator of AMPK (Hawley,et al, Journal of Biology 2003, 2:28 and Shaw,et al, PNAS, vol. 101, no. 10, 3329-3335).

The breakthrough occurred in the laboratory of Jeffrey Pessin, Ph.D., the Judy R. and Alfred A. Rosenberg Professorial Chair in Diabetes Research and Director, Diabetes Research Center, Department of Medicine at the Albert Einstein College of Medicine.

Dr. Pessin and his team discovered that suppression of FYN kinase activates LKB-1, which in turn activates AMPK. 

In work described in Yamada, et al, Cell Metabolism 11, 113–124, February 3, 2010, Dr. Pessin and his team began their investigation on mice that lack the gene that encodes for FYN. 

AMPK phosphorylation & activation via activation of LKB1 results:


  • Energy expenditure
  • Insulin sensitivity
  • Fatty acid oxidation


  • Plasma and tissue lipids
  • Cholesterol
  • Fat mass


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