详细记录  
题名:AMP-activated protein kinase as regulator of P2Y(6) receptor-induced insulin secretion in mouse pancreatic beta-cells.
作者:BALASUBRAMANIAN R; MARUOKA H; JAYASEKARA PS; GAO ZG; JACOBSON KA;
来源:Biochem Pharmacol. 2013 Apr 1;85(7):991-8. doi: 10.1016/j.bcp.2012.11.029. Epub [ IF= 0.00 ] ]
URL :10.1016/j.bcp.2012.11.029
日期:20130131
摘要:5'-AMP-activated protein kinase (AMPK) and its pharmacological modulators have
been targeted for treating type 2 diabetes. Extracellular uridine 5'-diphosphate
(UDP) activates P2Y6 receptors (P2Y6Rs) in pancreatic beta-cells to release
insulin and reduce apoptosis, which would benefit diabetes. Here, we studied the
role of P2Y6R in activation of AMPK in MIN6 mouse pancreatic beta-cells and
insulin secretion. Treatment with a potent P2Y6R dinucleotide agonist MRS2957
(500nM) activated AMPK, which was blocked by P2Y6R-selective antagonist MRS2578.
Also, MRS2957 induced phosphorylation of acetyl-coenzyme A carboxylase (ACC), a
marker of AMPK activity. Calcium chelator BAPTA-AM, calmodulin-dependent protein
kinase kinase (CaMKK) inhibitor STO-069 and IP3 receptor antagonist 2-APB
attenuated P2Y6R-mediated AMPK phosphorylation revealing involvement of
intracellular Ca(2+) pathways. P2Y6R agonist induced insulin secretion at high
glucose, which was reduced by AMPK siRNA. Thus, P2Y6R has a crucial role in
beta-cell function, suggesting its potential as a therapeutic target in diabetes.

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