title: Activation of AMP-activated protein kinase mediates acute and severe hypoxic injury to pancreatic beta cells.
abstract: In islet transplantation, a substantial part of the graft becomes nonfunctional for several reasons including hypoxia. AMP-activated protein kinase (AMPK) in mammalian cells is a regulator of energy homeostasis, and is activated by metabolic stresses such as hypoxia. However, the role of AMPK in hypoxic injury to pancreatic beta cells is not clear. When a rat beta cell line, INS-1 cell, was incubated in an anoxic chamber, phosphorylation of both AMPK and its downstream protein, acetyl-CoA carboxylase 2 increased with time. Adenovirus-mediated expression of constitutively active form of AMPK under normoxic conditions increased caspase-3 activation, suggesting induction of apoptosis. Reactive oxygen species production also increased with time during hypoxia. Pretreatment with compound C, an AMPK inhibitor, or N-acetyl-l-cysteine, an antioxidant, significantly lowered hypoxia-mediated cell death. These results suggest that AMPK, in association with oxidative stress, plays an important role in acute and severe hypoxic injury to pancreatic beta cells.
authors.affiliation: Division of Endocrinology & Metabolism, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Gyeong Ryul
authors.initials: GR
authors.lastname: Ryu
authors.forename: Min-Kyung
authors.initials: MK
authors.lastname: Lee
authors.forename: Esder
authors.initials: E
authors.lastname: Lee
authors.forename: Seung-Hyun
authors.initials: SH
authors.lastname: Ko
authors.forename: Yu-Bae
authors.initials: YB
authors.lastname: Ahn
authors.forename: Ji-Won
authors.initials: JW
authors.lastname: Kim
authors.forename: Kun-Ho
authors.initials: KH
authors.lastname: Yoon
authors.forename: Ki-Ho
authors.initials: KH
authors.lastname: Song
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000096:biosynthesis*; D000818:Animals; D017209:Apoptosis; D002460:Cell Line; D004789:Enzyme Activation; D000860:Hypoxia / Q000201:enzymology* / Q000473:pathology; D050417:Insulin-Secreting Cells / Q000201:enzymology* / Q000473:pathology; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species; D055372:AMP-Activated Protein Kinases