The protein kinase and tumor suppressor LKB1 is a potential activator of the adenosine monophosphate (AMP)-activated protein kinase (AMPK), a kinase that senses cellular energy levels by binding the metabolite AMP. Shaw et al. engineered mice so that LKB1 expression could be acutely blocked only in the liver and found that its expression plays a critical role in the control of metabolism in the liver and in glucose homeostasis. In the absence of LKB1, AMPK was almost completely inactive. Animals lacking LKB1 in the liver showed hyperglycemia and increased expression of genes encoding enzymes of gluconeogenesis and lipogenesis.
R. J. Shaw, K. A. Lamia, D. Vasquez, S.-H. Koo, N. Bardeesy, R. A. DePinho, M. Montminy, L. C. Cantley, The kinase LKB1 mediates glucose homeostasis in liver and therapeutic effects of metformin. Science 310, 1642-1646 (2005). [Abstract] [Full Text]