TY - JOUR
T1 - Mitochondrialuncouplingprotein-2isnotinvolvedin
palmitate-induced impairmentofglucose-stimulatedinsulinsecretion
in INS-1Einsulinomacellsandisnotneededfortheamplification of
insulin release
AU - hirschberg, jensen V
AU - Affourtit, Charles
PY - 2015/3/27
Y1 - 2015/3/27
N2 - WehaverecentlyshownthatovernightexposureofINS-1Einsulinomacellstopalmitateinthepresence
of highglucosecausesdefectsinbothmitochondrialenergymetabolismandglucose-stimulatedinsulin
secretion (GSIS).Herewereportexperimentsdesignedtotesttheinvolvementofmitochondrial
uncoupling protein-2(UCP2)intheseglucolipotoxiceffects.Measuringreal-timeoxygenconsumption
in siRNA-transfectedINS-1Ecells,weshowthatdeleteriouseffectsofpalmitateontheglucosesensitivity
of mitochondrialrespirationandonthecouplingefficiency ofoxidativephosphorylationareindepen-
dent ofUCP2.Consistently,palmitateimpairsGSIStothesameextentincellswithandwithoutUCP2.
Furthermore,weknockeddownUCP2inspheroidINS-1Ecellclusters(pseudoislets)totestwhetheror
not UCP2regulatesinsulinsecretionduringprolongedglucoseexposure.Wedemonstratethatthereare
no differencesintemporalGSISkineticsbetweenperifusedpseudoisletswithandwithoutUCP2.We
conclude thatUCP2isnotinvolvedinpalmitate-inducedimpairmentofGSISinINS-1Einsulinomacells
and isnotneededfortheamplification ofinsulinrelease.Theseconclusionsinformongoingdebateon
the disputedbiochemicalandphysiologicalfunctionsofthebetacellUCP2.
AB - WehaverecentlyshownthatovernightexposureofINS-1Einsulinomacellstopalmitateinthepresence
of highglucosecausesdefectsinbothmitochondrialenergymetabolismandglucose-stimulatedinsulin
secretion (GSIS).Herewereportexperimentsdesignedtotesttheinvolvementofmitochondrial
uncoupling protein-2(UCP2)intheseglucolipotoxiceffects.Measuringreal-timeoxygenconsumption
in siRNA-transfectedINS-1Ecells,weshowthatdeleteriouseffectsofpalmitateontheglucosesensitivity
of mitochondrialrespirationandonthecouplingefficiency ofoxidativephosphorylationareindepen-
dent ofUCP2.Consistently,palmitateimpairsGSIStothesameextentincellswithandwithoutUCP2.
Furthermore,weknockeddownUCP2inspheroidINS-1Ecellclusters(pseudoislets)totestwhetheror
not UCP2regulatesinsulinsecretionduringprolongedglucoseexposure.Wedemonstratethatthereare
no differencesintemporalGSISkineticsbetweenperifusedpseudoisletswithandwithoutUCP2.We
conclude thatUCP2isnotinvolvedinpalmitate-inducedimpairmentofGSISinINS-1Einsulinomacells
and isnotneededfortheamplification ofinsulinrelease.Theseconclusionsinformongoingdebateon
the disputedbiochemicalandphysiologicalfunctionsofthebetacellUCP2.
U2 - 10.1016/j.bbrep.2015.03.008
DO - 10.1016/j.bbrep.2015.03.008
M3 - Article
SN - 2405-5808
VL - 1
SP - 8
EP - 15
JO - Biochemistry and Biophysics Reports
JF - Biochemistry and Biophysics Reports
IS - 0
ER -
