杨梅黄酮通过Wnt通路改善细胞因子诱导的胰岛β细胞功能障碍的实验与研究.pdfVIP

UpregulationofWntsignalpathwaybymyricetinattenuatesβ-cell dysfunctioninducedbycytokines DING Ye DAIXiao-QianZHANGZhao-FengLIYong DepartmentofNutritionandFoodHygiene,SchoolofPublicHealth,PekingUniversity,Beijing, 100191,China Weexaminedtheeffectofmyricetinoncelldysfunctionincytokine-inducedpancreatic β cellsandassessedwhetherWntsignalpathwaywasthetargetofmyricetin.RIN-m5fβcells wereexposedtoacombinationoftumornecrosisfactor-α,interleukin-1β,andinterferon-γ,withor withoutmyricetinpretreatmentfor48h.Thecellviability,basalandglucose-stimulatedinsulin secretionandWnt-signalingproteinswereevaluatedwithMTTassay,radioimmunoassayand westernblotting. The48hmultiple-cytokinetreatmentdecreasedcell viabilityand glucose-stimulatedinsulinsecretion,whileincreasingbasalinsulinsecretion.Westernblot analysisshowedthatWnt-signalingproteinsweredecreasedincytokine-treatedRIN-m5fcells. However,myricetinpretreatmentprotectedagainstcytokinesinducingcelldeath.Inaddition, myricetin (20 tmol/L) obviously decreased basal insulin secretion and increased glucose-stimulatedinsulinsecretionincytokine-treatedRIN-m5fcells.Westernblotanalysis showedthatWnt-signalingproteinswereincreasedaftermyricetinpretreatment.Therefore, myricetinmightattenuatecelldysfunctionincytokine-inducedRIN-m5FcellsviatheWntsignal pathway,andtheWntsignalpathwaymightbeusedasanewtargetforprotectingpancreaticβ cellsagainstcytokine-inducedcelldysfunctionanddeath. myricetin;cytokine;Wntsignalpathway;pancreaticβcells ~ ~ ~111~, ~ ~L)wasadded sremovedand eabsorbance~ ,l*.~ vo~,vl~. ~ ~yricetinhad ficantlyenh~ Iviability /-,-~.~//z)puu~ ayricetinwasprel eatedcells,basal ~0+1.8696)~tUl/ ;d[(37.45164-2.1 ~np-GSK3[I samplewasst PDH protein ~reeindepende .lll~.Jtl~:~ll1.111~~1.~.| iehGSK31~i: fittedbyana~ oftheprotel :ersthenuclet enin/TCFdow ~~l,-,~l~_C,~l-~, ~buted