ADP receptor P2Y(13) induce apoptosis in pancreatic beta-cells.

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

Abstract

Pancreatic beta-cell loss represents a key factor in the pathogenesis of diabetes. Since the influence of purinergic signaling in beta-cell apoptosis has not been much investigated, we examined the role of the ADP receptor P2Y(13) using the pancreatic insulinoma-cell line MIN6c4 as a model system. Real time-PCR revealed high expression of the ADP receptors P2Y(1) and P2Y(13). Adding the ADP analogue, 2MeSADP, to MIN6c4 cells induced calcium influx/mobilization and inhibition of cAMP production by activation of P2Y(1) and P2Y(13), respectively. 2MeSADP reduced cell proliferation and increased Caspase-3 activity; both these effects could be fully reversed by the P2Y(13) receptor antagonist MRS2211. We further discovered that blocking the P2Y(13) receptor results in enhanced ERK1/2, Akt/PKB and CREB phosphorylation mechanisms involved in beta-cell survival. These results indicate that P2Y(13) is a proapoptotic receptor in beta-cells as the P2Y(13) receptor antagonist MRS2211 is able to protect the cells from ADP induced apoptosis.

Detaljer

Författare
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Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Cellbiologi
Originalspråkengelska
Sidor (från-till)445-453
TidskriftCellular and Molecular Life Sciences
Volym67
StatusPublished - 2010
PublikationskategoriForskning
Peer review utfördJa

Relaterad forskningsoutput

Tan, C., 2012, Department of Cardiology, Clinical sciences, Lund University. 85 s.

Forskningsoutput: AvhandlingDoktorsavhandling (sammanläggning)

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