Activation of AMP-activated protein kinase mediates acute and severe hypoxic injury to pancreatic beta cells |
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Authors: | Gyeong Ryul Ryu |
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Institution: | Division of Endocrinology & Metabolism, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea |
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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. |
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Keywords: | Hypoxia Islet transplantation AMP-activated protein kinase Oxidative stress |
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