Shotaro Umezawa *, Takuma Higurashi and Atsushi Nakajima Pages 3629 - 3644 ( 16 )
Background: AMP-activated protein kinase (AMPK) is a protein kinase that maintains homeostasis in cells and organs. As a master regulator of metabolism, AMPK coordinates many metabolic reactions. AMPK is a key factor in diabetes and metabolic syndrome associated with dysregulation of the metabolic status. Recently, AMPK has also attracted attention as a tumor suppressor. The aim of this article is to discuss about the role of AMPK in diabetes as well as cancer and to evaluate its effectiveness in treatment and prevention of these diseases. </P><P> Method: We reviewed studies of signaling mechanism involving AMPK and research on the role of AMPK in human disease including diabetes and cancer. In particular, we focused our attention on clinical trials about cancer treatment and prevention targeting AMPK. </P><P> Results: Many experimental studies reported the relation of AMPK and various metabolic reactions, mainly regulating energy homeostasis. Recent studies showed effect of AMPK on arrest of cell cycle as well as suppression of inflammation, which are important factors for carcinogenesis. Although some clinical studies investigated cancer treatment and prevention targeting AMPK, the effective yields in clinical trial have been limited. </P><P> Conclusion: AMPK activation as represented by metformin showed to improve disorders associated with diabetes and metabolic syndrome and became a well-established treatment strategy for these diseases. The increasing evidence suggests that AMPK is a promising target in the treatment and prevention of cancer. Further investigation including long-term clinical trials with large sample size is needed.
AMPK, diabetes, metabolic syndrome, cancer, chemoprevention, metformin, biguanide.
Department of Gastroenteroloy and Hepatology, Yokohama City University School of Medicine, Yokohama, Department of Gastroenteroloy and Hepatology, Yokohama City University School of Medicine, Yokohama, Department of Gastroenteroloy and Hepatology, Yokohama City University School of Medicine, Yokohama