Genipinisacellpermeableinhibitorofuncouplingprotein2(UCP2).

Genipinstimulatsglucoseuptakeinatime-anddose-dependentmanner.Themaximaleffectisachievedat2 hwithaconcentrationof10 μM.Inmyotubes,genipinpromotesglucosetransporter4(GLUT4)translocationtothecellsurface,whichincreasesthephosphorylationofinsulinreceptorsubstrate-1(IRS-1),AKT,andGSK3β.Meanwhile,genipinincreasesATPlevels,closedKATPchannels,andthenincreasestheconcentrationofcalciuminthecytoplasminC2C12myotubes.Genipin-stimulatedglucoseuptakecouldbeblockedbyboththePI3-KinhibitorwortmanninandcalciumchelatorEGTA.Moreover,genipinincreasesthelevelofreactiveoxygenspeciesandATPinC2C12myotubes^[1].Genipinincreasesmitochondrialmembranepotential,whichthenincreasesATPlevelsandclosesKATPchannels,therebystimulatinginsulinsecretioninpancreaticβ-cells.Genipinactivatesglucose-excitedPOMCneurons^[2].Cytochromeccontentincreasessignificantlyinthecytosolofgenipin-treatedFaOcells.Activationofcaspase-3andcaspase-7isultimatelyresponsIBLeforgenipin-inducedapoptoticprocessinhepatomacells.ROSlevelnotablyincreasesinHep3Bcellstreatedwith200μMgenipin^[3].

• [1].MaC,etal.GenipinstimulatesglucosetransportinC2C12myotubesviaIRS-1andcalcium-dependentmechanism.JEndocrinol.2012Dec20.

  [2].PartonLE,etal.GlucosesensingbyPOMCneuronsregulatesglucosehomeostasisandisimpairedinobesity.Nature.2007Sep13;449(7159):228-32.

  [3].KimBC,etal.Genipin-inducedapoptosisinhepatomacellsismediatedbyreactiveoxygenspecies/c-JunNH2-terminalkinase-dependentactivationofmitochondrialpathway.BiochemPharmacol.2005Nov1;70(9):1398-407.

Briefly,thepeptidesubstrateN-acetyl-Asp-Glu-Val-Asp-ρ-nitroanilide(Ac-DEVD-ρNA)isaddedtothecelllysatesinassaybuffer(50mMHEPES,pH7.4,100mMNaCl,0.1%CHAPS,10mMdithiothreitol,1mMEDTA,10%glycerol)andincubatedat37°C.Thecleavageofthesubstrateismonitoredat405nm.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.

• [1].MaC,etal.GenipinstimulatesglucosetransportinC2C12myotubesviaIRS-1andcalcium-dependentmechanism.JEndocrinol.2012Dec20.

  [2].PartonLE,etal.GlucosesensingbyPOMCneuronsregulatesglucosehomeostasisandisimpairedinobesity.Nature.2007Sep13;449(7159):228-32.

  [3].KimBC,etal.Genipin-inducedapoptosisinhepatomacellsismediatedbyreactiveoxygenspecies/c-JunNH2-terminalkinase-dependentactivationofmitochondrialpathway.BiochemPharmacol.2005Nov1;70(9):1398-407.

226.23

C₁₁H₁₄O₅

6902-77-8

4°C,protectfromlight

RoomtemperatureincontinentalUS;mayvaryelsewhere

DMSO:≥210mg/mL

*"<1 mg/ml"="" means="" slightly="" soluble="" or="" insoluble.="" "≥"="" means="" soluble,="" but="" saturation="">