Investigators at the Hebrew University of Jerusalem (Israel) worked with a line of mice that specifically lacked beta cell LKB1 (serine/threonine kinase 11). This enzyme is a primary upstream kinase of adenine monophosphate-activated protein kinase (AMPK), a necessary element in cell metabolism that is required for maintaining energy homeostasis. LKB1 exerts a growth suppressing effect by activating a group of approximately 14 other kinases, comprising AMPK, and AMPK-related kinases. Activation of AMPK by LKB1 suppresses growth and proliferation when energy and nutrient levels are scarce.

Results published in the October 7, 2009, issue of the journal Cell Metabolism revealed that deletion of the LKB1 gene from beta cells caused the production and secretion of more insulin than normal beta cells, resulting in an enhanced response to increases in blood glucose levels. Additionally, LKB1 deficiency caused a 65% increase in beta cell volume.

While it is attractive to speculate that it may be possible to develop some type of novel therapy for diabetes based on limiting the presence of this gene in pancreas beta cells, thus enhancing insulin secretion; it is necessary to recognize the role of LKB1 as a tumor suppressor gene. Activation of AMPK-related kinases by LKB1 is important for maintaining cell polarity thereby inhibiting inappropriate expansion of tumor cells, while loss of LKB1 leads to disorganization of cell polarity and facilitates tumor growth under energetically unfavorable conditions.

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Hebrew University of Jerusalem