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bythePancreas1
,GIORGIOGALANSIN02ANDERMINIOCOSTA3
FromdheDepartmentofPhysiologyandPharmacology,TheChicagoMedicalSchool,Chicago12,Illinois
NDERcertainexperimentalconditions,animalprolactinmaystimulatethesecretion
prolactinhasadiabetogenicactionofanti-insulinhormonesofpituitary,adrenal
U(1-4)whichseemstobeaccompa-
niedbyadecreasedinsulincontentofthepan-thispaperwasdesignedtostudytheeffects
creas(5).Experimentsperformedinthislabo-ofprolactinonthesecretion(orliberation)of
ratory(6)havedemonstratedthatthefirstinsulinandofglucagonbythepancreas.
injectionofprolactininnormaldogscauses
aloweringofthebloodsugarassociatedwithMETHODS
amarkeddegranulationoftheBcellsoftheTheproblemwasinvestigatedbymeansof18cross-
circulationexperiments,using36healthymongreldogs
isletsofLangerhansandthatrepeatedin-
jectionsarefollowedbyhyperglycemiawithhoursbeforetheexperiment,wereanesthetizedwith
(35mg/kgintraperitoneally),
depancreatizeddogs,prolactinalwayscausesheparinizedsandpreparedasdescribedinprevious
,al-papers(9-1I).In15experiments,thepancreatic-duo-
denalveinofadonordogDwasconnectedwitha
thoughprolactinitselfmayhaveahypergly-
cemiceffect,itsinjectionintoanormaldog,wereofthreetypes:infiveexperiments,untreated
forthefirsttime,causestheliberationofpre-donordogsreceivedanintravenousinjectionofpro-
formedinsulininamountssufficienttolowerlaCtin5(ArmourLot%4911~4;20m/kg),atotime;
infiveexperiments,thedonordogsreceivedthreepro-
injections,theactivityoftheBcellsisreducedandafourthoneduringtheexperiment,atotimein
andprolactinhyperglycemianolongercanbefiveexperiments,untreateddonordogsreceivedIuof
,in-PituitrinS,anamountsimilartothatpresentasim-
-
sulincouldnotbesecretedatallandhyper-ingthreeexperiments,theanastomosiswasmadebe-
glycemiawouldresult,
,untreateddonors
time,althoughitsoccurrenceinhypophysec--
minedinduplicatewiththemethodofNelson(I2).The
tomized,adrenalectomizedanddepancreatizedstatisticalsignificanceoftheresultswascalculated
animals(3-6)suggeststhat,likeanteriorpitu-accordingtoFisher(13).
itarygrowth(diabetogenic)hormone(7,s>,
prolactinmayactdirectlyontheuptakeofRESULTS
theadditionalpossibilitythatinthenormalaveragechangesintheconcentrationofblood
glucosecomparedtothepre-injectionvalues.
ReceivedforpublicationMarch17,1955.
FigureIrepresentsthechangesinbloodsugar
lThesestudieswereaidedbygrantsfromtheUnited
-observedinfivepancreatic-femoralcross-circu-
-
-treateddonordogsreceivedaninjectionof
dress:IstitutodiAnatomiaPatologica,
Milano,Italy.
3ResearchFellow(Fulbright).Permanentaddress:precedingtheinjection,therewerenosignifi-
IstitutodiFarmacologia,UniversithdiCagliari,Italy.
4Theproductionofpermanentdiabetesbypro-,
longedtreatmentwithprolactinhasnotbeenat--
,
${}${}()onDecember23,2018.
,
P-PROLACTINP-PROLACTIN
D-ANIMALSD-ANIMALS
DiSCONNECTEDDISCONNECTED
O-DONOR
O-DONOR
O-RECIPIENT
II1
QL-40’
5-600+60+120+1803-600t60+120+180
MlNUfESMINUTES
FIG,
-femoralanastomosis,Fiveexperi---
.
cantchangesinthebloodsugarofeitherdugDDISCUSSION
intodogD,thebloodsugarofbothdogsbeganobservedindogsDandRfollowingthefirst
todeclinesignificantly(P<)reachingainjectionofprolactinintodogDisduetothe
minimumafterabout45minutesintherecip-secretionortotheliberationofinsulinbythe
ient,andcontinuingtodeclineafterinterrup-pancreasofdogDandtoitspartialtransfer
-femoralanas-
zrepresentstheresultsofthreecontrolmesen-
teric-femoralcross-(6),this
theseexperiments,theinjectionofprolactinhypoglycemiaprobablyisduetoliberationof
intopreviouslyuntreateddonordogsagainpreformedinsulinratherthantoitsincreased
causedamarkedandsignificant(P<)
hypoglycemia,butinthiscase,thebloodsugaritimprobablethatthefallinbloodsugarof
oftherecipientdogsremainedessentiallydugRisduetotransferofsignificantamounts
:a)the
Rreceivingmesenteric
obtainedinfivepancreatic-femoralcross-circu-bloodsugarofdug
insteadofpancreaticbloodremainsunchanged,
lationexperimentsinwhichdonordogsprevi-
andb)thebloodsugarofdogRreturnstoward
ouslytreatedwithprolactinreceivedanaddi-
normalshortlyaftertheflowofinsulin-carry-
ingpancreaticbloodfromdogDisinterrupted,
experiments,prolactincausedamarkedandwhilethebloodsugarofdogD,whichisunder
significant(P<)hyperglycemiaindogDtheinfluenceofprolactin,continuestofall.
accompaniedbyamoderateandpossiblysig-Afterrepeatedinjections,prolactincausesa
nificant(P=)
-
fivepancreatic-femoralcross-circulationexper-geststhatthehyperglycemiaofdogDisnot
imentsinwhichuntreateddonorsreceivedantheresultofanincreasedsecretionorlibera-
,onthecontrary,
inthebloodsugarofdogDandonlyamoder-itisaccompaniedbythesecretionofsmall
ateandpossiblysignificant(P=)hypo-amountsofinsulincoincidentwiththepartial
(6).Partof
${}${}()onDecember23,2018.
PROLACTINANDINSULINSECRETION495
w+40
P-PlTUITRlN-S
08
DISCONNECT‘ED3D-ANIMALS
WDlSCONNECTED
+20
3-600t60t120t180
MINUTESMINUTES
-
Donordogspretreatedwithprolactin,recipientdogsun--
--experiments.
ments.
thisinsulinistransferredtodogRwhereitdenalormesentericveinofthedonordogD
causeshypoglycemia,
counteractthehyperglycemiceffectofprolac-intravenousinjectionofprolactinintoprevi-
-
inthepancreaticbloodofdogstreatedwithingofthebloodsugarassociatedwiththe
prolactin,controlmesenteric-femoralcross-cir-appearanceofahypoglycemicmaterial(in-
culationexperimentswithpretreateddonorssulin),butnot
posteriorpituitaryhormonesalsomaycausethroughtheanastomosisandcauseshYPoglY-
hyperglycemia(7,14).
elevationinbloodsugarcanbeobtainedonlyindonordogspreviouslytreatedwithrepeated
thanthosecontainedintheprolactinprepara-material(glucagon)appearsinthepancreatic
tionused,thepossibleinfluenceoftheseim-
puritiesontheresultswasinvestigatedandthehypothesisthattheso-calleddiabetogenic
ruledoutbytheexperimentswithPituitrineffectofprolactinmaybetheresultofarapid
andbycontrolexperimentswithACTHpre-dumpingofpreformedinsulinbytheBcells
viouslyreported(6).Similarly,anyeffectsofoftheisletsofLangerhansfollowedbyde-
outbytheresultsofthemesenteric-femoralsuggeststhatprolactindoesnotcausean
cross-circulationexperimentsandofexperi-increaseinglucagonsecretion.
mentswithsalinepreviouslyreported(9).TheREFERENCES
slightfallinthebloodsugarofdogRfollowing
,
theinjectionofPituitrinintodogDoccurs
45:627,=949*
alsoaftertheinjectionofsaline(9),.
:roe,1953.
,
:23,1953.
SUMMARYANDCONCLUSIONS4,HOUSSAY,.,-
:33,1953.
Eighteencross-,C.,,.
performedanastomosingthepancreatic-duo-:260,1951.
${}${}()onDecember23,2018.
&
,.,,,.,,,GLASSIAANAND
:313,,;..&A&:
,:758,=953*
471,I953-,:375,1944.
,:649,
,&s&xlMethodsj’wResearchWork-
*9s*
,.,:Oliver&Boyd,Ltd.,1938.
:197,,.,,,-
,.,,H,,,,~.
:32,UzcmavtPj?ys%‘uZogy(2nded,).NewYork:McGraw-
1952*Hill,1955,p*4239
${}${}()onDecember23,2018.
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