Activation of AMP-activated protein kinase mediates acute and severe hypoxic injury to pancreatic beta cells.
Activation of AMP-activated protein kinase mediates acute and severe hypoxic injury to pancreatic beta cells.
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DOI：
10.1016/j.bbrc.2009.06.039
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发表时间：
2009-08
影响因子：
3.1
通讯作者：
G. Ryu;Min-Kyung Lee;Esder Lee;Seung-Hyun Ko;Y. Ahn;Ji‐Won Kim;K. Yoon;K. Song
中科院分区：
文献类型：
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作者：
G. Ryu;Min-Kyung Lee;Esder Lee;Seung-Hyun Ko;Y. Ahn;Ji‐Won Kim;K. Yoon;K. Song
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.
