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Type 1 diabetes is caused by autoimmune destruction of pancreatic beta cells, possibly virus initiated. Virus infection induces alpha-interferon (IFN- α ), leading to upregulation of genes encoding double-stranded (ds) RNA-dependent antiviral enzymes 2′, 5′-oligoadenylate synthetase (2′5′AS) and PKR (p68). To investigate whether beta cell specificity could be due to antiviral differences between beta and alpha cells, we treated beta and alpha TC3 cell lines with IFN- α  and/or poly(I:C) (a synthetic dsRNA). Results showed that, following IFN- α  stimulation, increases in 2′5′AS levels and activities were significantly higher in beta than alpha cells ( P  < .001), whereas increases in PKR level and activity were comparable in the two cell types. Poly(I:C) stimulated 2′5′AS activity in beta but not alpha cells, and co-transfection IFN- α  plus poly(I:C) induced apoptosis in beta but not alpha cells. These findings suggest that the elevated 2′5′AS response of pancreatic beta cells could render them particularly vulnerable to damage and/or apoptosis during virus infection.

experimental diabetes research

Murine Pancreatic Beta TC3 Cells Show Greater<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:msup><mml:mtext>2</mml:mtext><mml:mo>′</mml:mo></mml:msup><mml:mo>,</mml:mo><mml:msup><mml:mtext>5</mml:mtext><mml:mo>′</mml:mo></mml:msup></mml:mrow></mml:math>-Oligoadenylate Synthetase (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:msup><mml:mtext>2</mml:mtext><mml:mo>′</mml:mo></mml:msup><mml:msup><mml:mtext>5</mml:mtext><mml:mo>′</mml:mo></mml:msup…

Murine Pancreatic Beta TC3 Cells Show Greater2′,5′-Oligoadenylate Synthetase (2′5′