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Inhibition of AMP-activated protein kinase protects pancreatic beta-cells from cytokine-mediated apoptosis and CD8+ T-cell-induced cytotoxicity.


ABSTRACT:

Objective

Apoptotic destruction of insulin-producing pancreatic beta-cells is involved in the etiology of both type 1 and type 2 diabetes. AMP-activated protein kinase (AMPK) is a sensor of cellular energy charge whose sustained activation has recently been implicated in pancreatic beta-cell apoptosis and in islet cell death posttransplantation. Here, we examine the importance of beta-cell AMPK in cytokine-induced apoptosis and in the cytotoxic action of CD8(+) T-cells.

Research design and methods

Clonal MIN6 beta-cells or CD1 mouse pancreatic islets were infected with recombinant adenoviruses encoding enhanced green fluorescent protein (eGFP/null), constitutively active AMPK (AMPK-CA), or dominant-negative AMPK (AMPK-DN) and exposed or not to tumor necrosis factor-alpha, in

SUBMITTER: Riboulet-Chavey A 

PROVIDER: S-EPMC6101197 | biostudies-literature | 2008 Feb

REPOSITORIES: biostudies-literature