AMP-activated protein kinase attenuates nitric oxide-induced beta-cell death.

The Journal of Biological Chemistry
Gordon P MearesJohn A Corbett

Abstract

During the initial autoimmune response in type 1 diabetes, islets are exposed to a damaging mix of pro-inflammatory molecules that stimulate the production of nitric oxide by beta-cells. Nitric oxide causes extensive but reversible cellular damage. In response to nitric oxide, the cell activates pathways for functional recovery and adaptation as well as pathways that direct beta-cell death. The molecular events that dictate cellular fate following nitric oxide-induced damage are currently unknown. In this study, we provide evidence that AMPK plays a primary role controlling the response of beta-cells to nitric oxide-induced damage. AMPK is transiently activated by nitric oxide in insulinoma cells and rat islets following IL-1 treatment or by the exogenous addition of nitric oxide. Active AMPK promotes the functional recovery of beta-cell oxidative metabolism and abrogates the induction of pathways that mediate cell death such as caspase-3 activation following exposure to nitric oxide. Overall, these data show that nitric oxide activates AMPK and that active AMPK suppresses apoptotic signaling allowing the beta-cell to recover from nitric oxide-mediated cellular stress.

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Citations

Jan 5, 2011·The Journal of Biological Chemistry·Katherine J HughesJohn A Corbett
Sep 8, 2011·Molecular and Cellular Biology·Gordon P MearesJohn A Corbett
Jun 21, 2011·American Journal of Physiology. Heart and Circulatory Physiology·Anne R DiersNeil Hogg
Oct 25, 2012·Endocrinology·Theodore C FriedmanAmiya P Sinha-Hikim
Jan 17, 2013·American Journal of Physiology. Endocrinology and Metabolism·Gordon P MearesJohn A Corbett
Apr 3, 2015·Stem Cells Translational Medicine·Erin M KroppRebekah L Gundry
Oct 6, 2017·Antioxidants & Redox Signaling·Bryndon J Oleson, John A Corbett
May 18, 2016·Molecular and Cellular Biology·Bryndon J OlesonJohn A Corbett
Dec 7, 2018·Journal of Neurochemistry·Neil T SprenkleGordon P Meares
Jan 10, 2020·The Journal of Biological Chemistry·Zachary R ShaheenJohn A Corbett
Jan 18, 2013·Annals of the New York Academy of Sciences·Lindsey E PadgettHubert M Tse
Mar 4, 2015·International Journal of Cancer. Journal International Du Cancer·Orianne Olivares, Sophie Vasseur
Jun 27, 2019·Molecular and Cellular Biology·Bryndon J OlesonJohn A Corbett

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