Katrina MacAulay1, James R Woodgett. 1. Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario M5G 1X5, Canada.
Abstract
BACKGROUND: In spite of its rather specific name, glycogen synthase kinase-3 (GSK-3) is an eclectic cellular regulator that modulates an array of processes from nuclear transcription, to neurological functions and metabolism. The enzyme is also a focal point for diverse signaling pathways that act to suppress its activity. OBJECTIVES: To review recent evidence supporting the important role GSK-3 plays in glucose homeostasis and discuss the therapeutic potential of inhibiting this enzyme in the treatment of diabetes and insulin resistance. RESULTS/ CONCLUSION: Despite its pleiotropic nature, GSK-3 has significant promise as a target for diabetes due to functional partitioning of the enzyme, tissue-selectivity and acute dosage-dependency of effects of inhibition, suggesting useful therapeutic windows.
BACKGROUND: In spite of its rather specific name, glycogen synthase kinase-3 (GSK-3) is an eclectic cellular regulator that modulates an array of processes from nuclear transcription, to neurological functions and metabolism. The enzyme is also a focal point for diverse signaling pathways that act to suppress its activity. OBJECTIVES: To review recent evidence supporting the important role GSK-3 plays in glucose homeostasis and discuss the therapeutic potential of inhibiting this enzyme in the treatment of diabetes and insulin resistance. RESULTS/ CONCLUSION: Despite its pleiotropic nature, GSK-3 has significant promise as a target for diabetes due to functional partitioning of the enzyme, tissue-selectivity and acute dosage-dependency of effects of inhibition, suggesting useful therapeutic windows.
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