670
3162046470016778155
Khawla7545880234165313450640748886
Al-Ali16985880234138246296434542594
Department754802014981156232313348384495569643679
of1470802014975112
Pharmacology1618802014959129210244355436505580600675756815
College754946014989164183203277358433
of1224946014975111
Medicine13729460149110184264284353373446521
&1929946014976
Health2042946014973148229248284354
Sciences2432946014955124143218291360434479
Dissertation7521299017098132193255344389431524566599689773
Title75214940122426696120184
Effects1783149601205385116181246280319
of2129149601206697
Exercise22541496012053101166197261281320385
and26671496012068129198
Pharmacological28921496012059120189219313381446511531597664684749817837
Intervention3757149601202283117182212268333394428448513574
on43591496012065126
Electromechanical4513149601205474139203237267333427491556617685746766831900920
Function54601496012049109171235269289355416
of5903149601206697
the6028149601203495160
Heart17831616012068133202232266
in2076161601202081
the2185161601203495160
Goto-Kakizaki23731616012087152186252285344412462482525593644664
Type3064161601204396165230
233211616012056
Diabetic3404161601207595163231296330350415
Rat38471616012060129162
Faculty7521769012248114178238262292350
Advisor11301769012274140196220264328360
Professor1783177101205989154186251290328394424
Frank2235177101204878147208258
Christopher25201771012082143173193232266331399460525555
Howarth31031771012068134217285315349410
Defense7521924012270134162226286330394
Date11741924012270136166230
1617831926012055111
June19221926012048109170235
201521841926012056111166222
Abstract7522239012274140184214246312376406
Type178322460963477132184
21989224609648
diabetes206322460965571125180232259311342
mellitus2431224609675127143159175202251282
(T2DM)273522460963367112171245274
accounts3035224609655107158211259308335366
for342322460962982106
more3555224609675127151203
than378022460963179134183
90%398522460964892154
of416522460965378
cases4269224609651106137189220
of451522460965278
diabetes461822460965571126180232260312343
mellitus.4986224609675127143159175203251282304
Cardiovascular5316224609665120144198214267311366397449497513568592
diseases593422460965571102154208239291322
are178323420965579130
the193623420962978130
major2090234209675130146198223
causes2337234209652106155186238269
of263123420965277
morbidity2733234209675127151206222276292320362
and3120234209654103158
mortality3303234209675127151178233249265292335
in366023420961867
diabetic375223420965470125180232259275326
patients.4103234209654109136152204253280311333
A4461234209659
variety4542234209647101125141193221263
of483023420965277
diastolic493223420965571125156183236252268320
and5276234209655103158
sys-tolic545623420963477108134161214230246298
dysfunctions577823420965598129154203251303330346399447478
have1783243809649103148200
been2005243809663115167216
reported.224324380963284138191215242294349371
The263624380964391143
severity280224380963991135187211227254297
of312224380966085
the323024380963584136
abnormalities3388243809663118166219243320375391407434450502533
depends3943243809663115170222271325356
on4322243809660109
the445324380963685137
patients’4612243809663117144160212261288319347
age4982243809663116168
and5173243809663111166
diabetes536124380966480134189241268320351
duration.5734243809663112136191218234286335357
The611324380964392144
aim178325340965571146
of195125340966591
the206425340964089141
study222725340964471120175218
was2467253409680134165
to265425340964193
investigate276925340963078123175206233249303357385437
the322825340964089141
age-dependent,3391253409668122174200255307362414462517569618645667
exercise4080253409666104156180231247278330
and4432253409668117172
drug462625340966892141195
interven-tion484325340962978105157181225277326353380396448497
on5362253409666115
electromechanical549925340966581133185212236288363415467516570619635687741757
function178326300962574123174201217270319
of212426300966287
the223326300963685137
heart2392263009658110165189216
in263026300962675
the272726300963685137
Goto-Kakizaki2896263009669122149201228275330370386420475515531
(GK)3449263009639109156185
type365726300963679134186
23865263009653
diabetic394126300966480134189241268284336
rat.429926300963488115138
mRNA4468263009675124183242
expres-sion4732263009662100155179230261288319335387436
was5200263009666121152
assessed537426300966495126178209240292347
in574326300962674
ventricular5840263009653105154181205221273322338392416
muscle1783272609675124155206222274
with207927260966682109158
real-time225927260962375129145172199215290342
RT-PCR.262227260964983110157222271293
Ventricular2936272609656100149176200216268316332387411
myocytes3368272609675118171222265292344375
shortening,376627260963078131155182234283299348401424
intracellu-lar42122726096146390114169221273289305354380396451475
Ca2+4708272609665120164212
transport494327260962650104153184239291315342
and5306272609655104159
L-type54872726096366289132187239
Ca2+5747272609665119164212
current5980272609652101125149201249276
were1783282209666118143194
measured2011282209675127181212261285337392
with242528220967894121170
video261728220965571126178231
edge2870282209663118172224
detection,3116282209666118145197249276292344393415
fluorescence35532822096315199152176227258310362411463515
pho-tometry4090282209666114167193221273348400427451494
and4606282209666115170
whole4798282209678127179195247
cell5067282209663115131147
patch5236282209666121148200249
clamp550728220966379133209263
techniques,579228220963991142191240256311359411442464
respectively.178329180962476107161213265292308353405421463486
In229129180961968
vivo238129180964662106159
biotelemetry256329180965571123150202218270345397424448491
was3078291809666121152
used325329180964980132187
to346229180962981
measure3566291809675127182213262286338
the392629180962877129
electrocardiogram407829180965268120172199223275327382406460476529583607661736
(ECG).483629180963174139209238261
In511929180961968
young520929180964497145194248
GK5481291809669117
(8-10562029180963175102146190
weeks)5834291809666118170210241271
rat,612729180962680107129
mRNA1783301409675124183242
expression204130140965290145169220251283299351400
of245730140965277
Atp1a3,255030140965986141185240284306
Cacna1h,2872301409665120171220275319368390
Scn1b,327830140964091140185239261
Hcn23555301409655107155200
were3770301409667119143195
up-regulated3980301409649104130154206260308324379406458513
and4509301409654103158
Slc9a1,468330140964056107152206251273
Hcn4,4972301409654106155199221
Kcna2/4,520930140964799148203247282326348
Kcnj2557330140964899148164209
were5797301409667119143195
downregulated.6007301409655108174223178331100962476130178194249276328383405
Amplitude2210311009669144198214230258306361413
of264531100966287
ventricular2754311009654106155182206222274323339393418
myo-cyte3203311009675118171197249292319371
shortening359631100964190142166193245294310359413
and4031311009664113168
intracellular422131100962574101125180232284300316364380435459
Ca2+4712311009665120164212
transient494631100963761116165196212264313340
were5317311009667119143195
unaltered,5534311009658107162178205257281332387409
time596531100963753128180
to616731100963790
peak1783320609655107161201
shortening200732060962675127152179231279295344398
was2423320609666121152
prolonged259332060965579131147199248302354409
and3019320609655104159
time320032060962339114166
to338832060962375
half3481320609649103119144
decay3643320609655107159214256
of391732060965378
the401732060962372124
Ca2+4158320609666120164213
transient439332060962347102150182198250298325
was4736320609667121152
shortened491132060962675128152179231280332386
in532032060961160
GK5398320609670117
myocytes.5533320609675118170222265292344375397
Physical594832060964796139170186238292308
exercise178333020965290142166218234265317
is212233020962455
well2208330209667119135151
established238133020966192119173228244260291340392447
as285033020966394
a2966330209663
valuable3052330209652107123172226281297349
form342333020963486110188
of363333020966186
non-pharmacological3741330209657110158185240288343367444499551603619672725741793848864
therapy.462733020963684136161215270313335
Experiments501533020965190144196220236311363412439470
were5516330209666118142194
performed5732330209663115139168221245322374429
in618333020962573
GK1783339809670117
and1922339809666115170
control2114339809663116165192216268284
(10-11242033980964185130156200245
months)2698339809676128177204253284313
following303333980963789105121174240256305359
2-3341433980965682127
months3574339809675128177204253284
of388033980966489
treadmill399133980963863114169224299315331347
exercise4360339809663102154178229245276328
training.471033980963963118134182198247301323
Expression505533980965593148172223254285301354403
of548033980966489
mRNA5602339809676124183242
encoding5867339809663112164216271287336389
Tpm2,178334940963489164208230
Gja4,204334940967086141185207
Atp1b1,227334940966794148193247292314
Cacna1g,2617349409665120171220275319373395
Cacnb2,3042349409665120172220275319341
Hcn2,3406349409662114163207229
Kcna33657349409656107156211255
and3934349409663112166
Kcne14123349409655107155207252
were4405349409666118142194
up-regulated4621349409657111138162214267316332387414466521
and5164349409662111166
Gja1,536034940967086141185207
Kcnj25589349409656107156172217
and5828349409662111166
Kcnk36016349409655107156196240
were1783359009666118143194
down-regulated2003359009655107174223249273325379427443498525577632
in265735900962069
hearts2748359009652104159183210241
of301535900965378
sedentary311535900963587141193242269324348391
GK3532359009670117
rats367135900962883110141
compared3834359009655108183237292316368423
to427935900963183
sedentary438435900963587142194243270324348391
controls.4797359009656108157184208260276307330
Gja1,515335900966986140185207
Cav35386359009665119164208
and5620359009655103158
Kcnk35800359009651103152192236
were6062359009667119143195
up-regulated1783368609649103130154206259308324379406458513
and2322368609655104158
Hcn22507368609655106155200
was2733368609667121152
down-regulated2912368609655107174223249273325379427443498525577632
in356636860962169
hearts3658368609653105159184211242
of392236860965782
exercise402636860965695147171222238269321
trained436936860963256111127176228282
GK4678368609670117
compared4817368609656109184238293317369424
to526336860963184
sedentary536936860963587142194243270325349392
GK5787368609670117
controls.5927368609656108157184208260276307329
Amplitude1783378209659134189205221248297351403
of220737820965277
ventricular230537820964496145172196212264312328383407
myocyte2732378209675118171223265293345
shortening,309937820962978130154181233282298347401423
Ca2+3542378209665120164213
transients377737820962549104153184200252301328359
and4156378209655104158
L-type43373782096356188131186238
Ca2+4595378209665120164213
current4828378209652100125149200249276
were5125378209666118142194
not5339378209649101128
significantly54903782096294599147163183202254309358385401444
altered.59543782096557198150174226280302
The178338780963483135
effects194038780966186111163215242273
of223538780966186
the234338780963685137
anti-diabetic2502387809663112139155182237253307362414441457509
drug303338780966387136190
Pioglitazone324538780965672124178194210237292326378427479
(PIO)374638780963886104173203
on3971387809661110
ventricular4103387809653105154181205221273321337392416
myocyte4550387809675118170222265292344
shorten-ing491638780964089141165192244293319335384438
and5376387809663112167
Ca2+5574387809665120164212
transport580838780963660115164195249302326353
in618338780962573
addition1783397409655109164180207223276325
to213039740962477
ECG2226397409643108178
were2423397409667119143194
also263739740965571102154
investigated.281339740961362107159190217233287341368420475497
PIO333039740964765135
(0.1-10)34873974096277193138164208253282
μM3789397409646119
reduced393139740962173127176228280335
the428839740962473125
amplitude4433397409654129184200216243292346398
of485139740965277
shortening495139740962877129153180232281297346400
in537339740961362
ventricular545439740964597146173197213264313329384408
myocytes5881397409675118171222265292344375
from178340700962549101176
GK1984407009670117
and2126407009654103158
control2308407009652105153180205257273
rats.260340700962681108139161
PIO278640700965068138
reduced294640700962678133182233285340
the330840700963079131
amplitude3463407009655130184200216244292347399
of388740700965277
the398640700963079131
Ca2+4141407009665120164213
transi-ent437640700962954108157188204231283331359
and4759407009655104158
modest4942407009675127182234265292
reductions525740700962678133181233260276328377408
in568740700961968
L-type57774070096396693136190242
Ca2+6044407009665120164212
current1783416609652100124149200249276
in208141660961766
GK2170416609670117
and2311416609654103158
control2492416609652104153180204256272
myocytes.2788416609675118170222265292344375397
Heart3208416609655107161185213
rate344341660962580107159
in362441660961766
GK3713416609670117
rats385241660962580107138
was4013416609667121152
reduced.418841660962577131180232284339361
Although457241660965975102151203252306355
PIO495041660964765135
reduced510741660962577132180232284339
blood546941660965571123175230
glucose572241660965470119171223254306
in605041660961766
GK6139416609670117
rats178342620962479106137
it194242620961946
had2010426209652107162
little2194426209619356289105157
effect237642620965277103155206233
on2634426209653102
heart2758426209652104158182209
ECG.2990426209645110180202
Research7094372017081171232322414459549633
Relevance13814372017081171204294372465549638728
and21484372017093177269
Potential24564372017079168210300384426459552585
Impact30814372017039170263355445487
Diabetes70945700966076130185237264316347
mellitus1077457009675127143159175202251282
is138145700961546
a1448457009654
serious152445700963082106122175223254
global179945700965470123177232248
and2068457009654103158
national2247457009649103130146199248302318
health2586457009649101156172199248
problem285545700965478130185201253328
and3204457009654103158
cardiovascular3383457009652106130185201253297352383435484500554578
complications3982457009652104179234250266318372400416468517548
are455145700965478130
the470345700962675127
major4851457009675130146198222
cause5094457009652107155186238
of535345700965378
morbidity5452457009675127151206222277293320363
and5835457009655104159
mortality6015457009675127151178233249265292335
in70946660961665
diabetic79646660966076131185237265281332
patients.1150466609661115142158210259286317339
Type151246660963982137189
21723466609650
diabetes179546660966076131186238265317348
mellitus2170466609675127143159175202251282
accounts2474466609660112164216265314341372
for286846660963183107
more3003466609675127151203
than322846660963381136185
90%343546660965094156
of361346660965883
cases3718466609658112143195226
of396746660965783
diabetes407246660966076131185237264316347
and4442466609660108163
cardiovascular4627466609658112136191207259303358389441489505560584
complications5233466609658110185240256272323378405421474522553
are580946660966084135
the596746660963281133
major6128466609675129145198222
cause709476209652106155186238
of96947620966287
morbidity1088476209675127151206222277293320363
and1473476209664112167
mortality1672476209675127151178233249265292335
in202947620962674
diabetic212647620966480134189241268284336
patients.2484476209664119146162214263290321343
Experiments284947620965291145197221237312364413440471
performed3342476209664116140169222246323375430
in379447620962574
this389047620963786102133
research404547620963385116168223247298347
project441447620966488140156208260287
have4723476209658113157209
provided495547620966388140184200255307362
further533947620963483107134183235259
clarification562047620966177132156172191211263317344360413462
of610447620966187
the621347620963685137
cellular709485809652104120136184200255279
and1006485809655104158
subcellular118748580962675130181233249265314330385409
basis1614485809654109140156187
of181948580965278
electromechanical191548580965268120171198222275350402453502557606622673728744
dysfunction267748580965598129154202251303330346399447
and3142485809655104159
the332348580962371123
effects346448580965278103155207234265
of374748580965277
exercise384248580965291143167218234265317
and4177485809655103158
drug435348580965579128182
intervention45574858096116087139163208260309336352404453
in503248580961261
type511548580962366120172
25305485809645
diabetic536848580965470125180232259275326
heart.5712485809649101156180207229
It596348580961441
is602748580961142
hoped6087485809649102156208263
that70949540962776131158
this8894954096297894125
mechanistic1039495409675127178227282331347378405421473
understanding1534495409651100154206230262289343392447463512566
will21244954096668298114
help2261495409651103119173
to245749540962981
facilitate256149540962782133149165181209263290342
the292649540962978130
development3080495409655107151203219272326401453502529
of363449540965277
new3734495409651103169
treatment392549540963054106160187262314363390
strategies43374954096346185140167219273289341372
for473149540962780104
this48574954096297894125
disease.500749540965470102154208239291313
Relevant7095060017081171204294372465549591
Publications13395060017078162255288322412504546580669753815
•709521809648
Salem80052180963892108160235
KA,1055521809648107129
Adrian1204521809659114138154209258
TE,14845218096327597
Qureshi1601521809670118142194225274290
MA,1911521809673133155
Parekh2086521809647102126178218267
K,237352180964769
Oz2462521809670104
M,258652180967396
Howarth2702521809654107173228252279328
FC.3052521809637102124
Shortening319852180963887139163190242291307356410
and3628521809654103158
intracellular38085218096146390114169220272288304353369424448
Ca2+4276521809665120164212
in451152180961462
ventricular459352180964597146173197213265313329384408
myocytes5021521809675118170222265292344375
and5416521809655104158
expression559552180965290145169220251282298351400
of601552180965277
genes6112521809654106155207238
encoding775531409652101153205260276325379
cardiac1176531409652106131185201255307
muscle1505531409675124155207223275
proteins180253140965579131158210226275306
in213053140961665
early2217531409652106130146189
onset2429531409652101132184211
type266253140962770125177
22861531409644
diabetic292753140965571126180232259275327
Goto-Kakizaki3276531409670122150202229276330371387421475515531
rats.383053140962478105136159
Exp401153140964381136
Physiol.416953140964796139170186238254276
2012446853140964488133177
Dec;4667531409660112163185
97487553140964488
(12):1281-91.498553140963074119148170215259303348374418463485
•709541009648
Salem80154100964095111163238
KA,1060541009648107129
Qureshi1211541009669118142194225274290
MA,1522541009674133155
Sydorenko169954100964083138190214266315355407
V,212854100965670
Parekh2219541009648102127178218267
K,250854100964769
Jayaprakash260054100963892135190244268323363418449498
P,312054100964759
Iqbal320154100961873127182198
T,342154100963448
Singh349154100963955104158207
J,372054100963860
Oz3802541009670104
M,392754100967496
Adrian4045541009659114138154208257
TE,43245410096347799
Howarth4445541009655107173228252279328
FC.4795541009639104126
(2012).494354100962973118162206236258
Effects52235410096436893145197224255
of550054100965277
exercise559954100965291143167218234265317
training593854100962751106122170186235289
on6249541009652101
excitation-contraction79855060965290142158185240267283335384410462515563591615669721748764817865
coupling1685550609652105153208224240289342
and2050550609654103158
related22305506096247692146173225280
mRNA2532550609675124183242
expression279655060965291145170221252283299352400
in321955060961664
hearts3306550609648100155179206237
of356555060965378
Goto-Kakizaki3665550609670122149202228276330370386420475515531
type421855060962770125177
24417550609644
diabetic448455060965470125180232259275326
rats.483355060962478105136159
Mol5014550609673126142
Cell5178550609665117133149
Biochem.534955060964662114166215267342364
201379856020964488133177
Aug;997560209659108162184
380120356020964489133
(1-2):135856020963074101145174197
83-96.157756020964488115159204226
•709569809648
Salem80356980964196112164239
KA,1065569809647107129
Jacobson121656980964094146199253284337385
M,162556980967395
Shafiullah174356980964189144164183232248264318367
M,213356980967496
Oz2253569809669103
M,237956980967496
Adeghate2499569809659114166219268323350402
E,292356980964466
Howarth3013569809654107173228252279328
FC.3363569809640105127
Effects35125698096447095147199226257
of379256980965378
pioglitazone389356980965571123177193209236291325377426478
on4394569809653101
electrical451956980965268120172199223239291345361
conduction4904569809651104153207256308335351403452
in537856980961766
the546656980962978130
Goto-Kakizaki5619569809670122149202228275330370386420475515531
type617256980962871126178
2709579409644
diabetic77757940965571125180232259275327
rat112657940962580107
heart1257579409648100155179206
(Accepted148557940963190142194246300328380434
in194257940961766
JCERC)2030579409640105148196261291
Career70959200170109202246336426470
Aspirations121959200170103165257291336428470504593677739
My709609809674116
aspirations84860980965485140156180235262278330379410
are128060980965579130
to143360980962779
acquire1534609809655107161210226250302
a1858609809654
PhD193560980964796155
degree2112609809655107161185237289
in242360980961665
Medical2510609809673125180196248303319
Sciences285160980964091107159208260312343
(Pharmacology321660980963077126180204282336388441457509563606
track)384460980962751106157198227
and4093609809655104158
then427460980962776128176
pursue4473609809654103127158206258
a4754609809654
research483060980962576107159214238289338
and709621409655103158
academic889621409655107161216268343359411
career.1322621409652107131182234258275
In161962140961867
the170862140962776128
long185862140961668117171
term205162140962779103181
I2254621409618
would2294621409666119167183238
like25546214096163273125
to270162140962779
heighten2802621409649101117171220247299348
awareness3172621409655121176200251300352383414
of360862140965378
the370862140962776128
importance385862140961691146198222249304353405457
of433762140965277
research443662140962476107159214238289338
in479662140961665
our4883621409652101125
community.709633009652104179254303352368395438460