详细记录  
题名:RFamide peptides 43RFa and 26RFa both promote survival of pancreatic beta-cells and human pancreatic islets but exert opposite effects on insulin secretion.
作者:GRANATA R; SETTANNI F; TROVATO L; GALLO D; GESMUNDO I; NANO R; GALLO MP; BERGANDI L; VOLANTE M; ALLOATTI G; PIEMONTI L; LEPRINCE J; PAPOTTI M; VAUDRY H; ONG H; GHIGO E;
来源:Diabetes. 2014 Mar 12. [ IF= 7.89 ] ]
URL :10.2337/db13-1522
日期:20140408
摘要:RFamide peptides 43RFa and 26RFa have been shown to promote food intake and to
exert different peripheral actions through GPR103 receptor binding. Moreover,
26RFa was found to inhibit pancreatic insulin secretion, whereas the role of
43RFa on beta-cell function is unknown, as well as the effects of both peptides
on beta-cell survival. Herein, we investigated the effects of 43RFa and 26RFa on
survival and apoptosis of pancreatic beta-cells and human pancreatic islets. In
addition, we explored the role of these peptides on insulin secretion and the
underlying signaling mechanisms. Our results show that in INS-1E beta-cells and
human pancreatic islets, both 43RFa and 26RFa prevented cell death and apoptosis
induced by serum starvation, cytokine synergism and glucolipotoxicity, through
PI3K/Akt- and ERK1/2-mediated signaling. Moreover, 43RFa promoted, whereas 26RFa
inhibited glucose- and exendin-4-induced insulin secretion, through Galphas and
Galphai/o proteins, respectively. Inhibition of GPR103 expression by small
interfering RNA blocked 43RFa insulinotropic effect, but not the insulinostatic
action of 26RFa. Finally, 43RFa, but not 26RFa, induced cAMP increase and glucose
uptake. In conclusion, because of their survival effects along with the effects
on insulin secretion, these findings suggest potential for 43RFa and 26RFa as
therapeutic targets in the treatment of diabetes.

================  评  论  部  分=================

重要性:
分类:(参照 Faculty of 1000 的分类体系)


评语:

评论密码:   返回前页  [全部]