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Finbarr P. M. O’Harte, Vadivel Parthsarathy, Christopher Hogg, Peter R. Flatt
Long-term treatment with acylated analogues of apelin-13 amide ameliorates diabetes and improves lipid profile of high-fat fed mice
www.plosone.org
www.plosone.org
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BT
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1 TL
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(8)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 525.77 312.0944 cm
BT
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1 TL
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1 TL
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ET
Q
q
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BT
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1 TL
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(8)Tj
ET
Q
q
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1 J
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BT
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2.3924 0 Td
(the)Tj
1.4683 0 Td
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3.7644 0 Td
(liraglutide)Tj
4.2917 0 Td
([)Tj
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(29)Tj
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(islets)Tj
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4.167 0 Td
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(30)Tj
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(once)Tj
2.1203 0 Td
(daily)Tj
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Q
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1 J
0 w
7.4999 0 0 6.6659 401.7826 238.507 cm
BT
/F7 1 Tf
1 TL
-0.0053 Tc
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(8)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 405.3543 234.085 cm
BT
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1 TL
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(GluPAL\)apelin-13)Tj
7.5684 0 Td
(amide)Tj
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Q
q
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1 J
0 w
7.4999 0 0 6.6659 562.2803 238.507 cm
BT
/F7 1 Tf
1 TL
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(8-)Tj
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Q
q
1 j
1 J
0 w
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BT
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1 TL
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(GluPAL\)apelin-13)Tj
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(amide)Tj
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1.0261 0 Td
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1.4683 0 Td
(GLP-1)Tj
2.8573 0 Td
(mimetic,)Tj
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(liraglutide)Tj
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(high-fat)Tj
3.3788 0 Td
(fed)Tj
1.457 0 Td
(mouse)Tj
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(diet-induced)Tj
5.3348 0 Td
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6.633 0 Td
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Q
q
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1 J
0 w
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BT
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1 TL
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(Materials)Tj
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Q
q
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BT
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1.1849 0 Td
(EZ)Tj
1.3889 0 Td
(Biolabs)Tj
3.1238 0 Td
(\(Carmel,)Tj
3.7417 0 Td
(IN,)Tj
1.525 0 Td
(USA\))Tj
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0 Tc
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(purity.)Tj
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(RP-HPLC)Tj
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(identity)Tj
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(electrospray)Tj
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4.0535 0 Td
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(28)Tj
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(].)Tj
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(of)Tj
1.0148 0 Td
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(apelin-13)Tj
3.9628 0 Td
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(enzyme)Tj
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(pro-)Tj
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(long)Tj
1.9842 0 Td
(the)Tj
1.4683 0 Td
(biological)Tj
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(activity.)Tj
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(a)Tj
0.6519 0 Td
(gamma-glutamyl)Tj
7.0356 0 Td
(spacer)Tj
2.7496 0 Td
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2.0012 0 Td
(palmitate)Tj
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Q
q
1 j
1 J
0 w
576 737.1 m
36 737.1 l
36 737.6 l
576 737.6 l
f*
36 741.2598 107.1496 23.6976 re
W* n
q
107.0929 0 0 23.6409 36 741.3165 cm
q
/I0 Do
Q
Q
Q
q
0 0 612 792 re
W* n
1 j
1 J
0 w
7.9999 0 0 7.9999 390.8976 745.7952 cm
BT
/F0 1 Tf
1 TL
-0.005 Tc
0 0 Td
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3.9897 0 Td
(apelin)Tj
2.8276 0 Td
(analogues)Tj
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(in)Tj
0.9851 0 Td
(obesity/)Tj
3.3803 0 Td
(diabetes)Tj
3.9331 0 Td
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Q
q
1 j
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576 48.0002 l
576 47.5002 l
36 47.5002 l
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81.5811 34.9228 m
237.8835 34.9228 l
h
f*
0 g
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BT
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2.8559 0 Td
(ONE)Tj
2.3669 0 Td
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(https://doi.or)Tj
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(g/10.137)Tj
3.8198 0 Td
(1/journal.po)Tj
5.1236 0 Td
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4.089 0 Td
(50)Tj
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2.0906 0 Td
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3.2882 0 Td
(29,)Tj
1.5874 0 Td
(2018)Tj
34.0302 0 Td
(2)Tj
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(/)Tj
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(17)Tj
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-66.402 84.0904 Td
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(analysis,)Tj
3.4087 0 Td
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1.2827 0 Td
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3.3733 0 Td
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3.3307 0 Td
(:)Tj
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0.4819 0 Td
(FOH,)Tj
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(PRF)Tj
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(and)Tj
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(Ulster)Tj
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3.3945 0 Td
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(:)Tj
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(EP2015/0592)Tj
5.0386 0 Td
(88\))Tj
1.474 0 Td
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2.9126 0 Td
(`Apelin)Tj
2.693 0 Td
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3.4512 0 Td
(s'.)Tj
1.0559 0 Td
(FOH)Tj
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(and)Tj
1.5874 0 Td
(PRF)Tj
1.7575 0 Td
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1.3677 0 Td
(inventors)Tj
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(originally)Tj
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4.7395 0 Td
(with)Tj
1.9956 0 Td
(the)Tj
1.4683 0 Td
(UK)Tj
1.6328 0 Td
(Animals)Tj
3.5773 0 Td
(\(Scientific)Tj
4.2462 0 Td
(Proce-)Tj
-34.9112 -1.2982 Td
(dures\))Tj
2.7722 0 Td
(Act)Tj
1.6214 0 Td
(1986)Tj
2.126 0 Td
(and)Tj
1.7291 0 Td
(EU)Tj
1.525 0 Td
(Directive)Tj
3.8835 0 Td
(2010/63EU)Tj
4.7111 0 Td
(for)Tj
1.389 0 Td
(animal)Tj
2.965 0 Td
(experiments)Tj
5.142 0 Td
(and)Tj
1.7292 0 Td
(approved)Tj
3.9741 0 Td
(by)Tj
1.1792 0 Td
(Ulster)Tj
-34.7468 -1.2983 Td
(University)Tj
4.3993 0 Td
(Animal)Tj
3.2201 0 Td
(Ethics)Tj
2.6702 0 Td
(Review)Tj
3.0955 0 Td
(Committee.)Tj
4.9606 0 Td
(All)Tj
1.4003 0 Td
(necessary)Tj
4.0195 0 Td
(steps)Tj
2.1826 0 Td
(were)Tj
2.1203 0 Td
(taken)Tj
2.4208 0 Td
(to)Tj
1.0261 0 Td
(prevent)Tj
3.2599 0 Td
(any)Tj
-34.7752 -1.3039 Td
(potential)Tj
3.7587 0 Td
(animal)Tj
2.9707 0 Td
(suffering.)Tj
ET
Q
q
1 j
1 J
0 w
11.9999 0 0 11.9999 200.0125 571.6913 cm
BT
/F11 1 Tf
1 TL
-0.0033 Tc
0 0 Td
(2.7.)Tj
1.7055 0 Td
(Statistical)Tj
4.3228 0 Td
(analysis)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 200.0125 554.6834 cm
BT
/F7 1 Tf
1 TL
-0.004 Tc
0 0 Td
(All)Tj
1.3946 0 Td
(data)Tj
1.9162 0 Td
(was)Tj
1.6951 0 Td
(analysed)Tj
3.651 0 Td
(with)Tj
1.9956 0 Td
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2.6022 0 Td
(\(v.5.0,)Tj
2.6418 0 Td
(GraphPad)Tj
4.303 0 Td
(Software)Tj
3.702 0 Td
(Inc.)Tj
1.7575 0 Td
(CA,)Tj
1.7972 0 Td
(USA\))Tj
2.4547 0 Td
(and)Tj
1.7292 0 Td
(expressed)Tj
4.0932 0 Td
(as)Tj
-35.7333 -1.2982 Td
(mean)Tj
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2.4434 0 Td
[()]TJ
/F7 1 Tf
0.788 0 Td
(S.E.M.)Tj
2.8347 0 Td
(Bodyweight,)Tj
5.1817 0 Td
(glucose,)Tj
3.4015 0 Td
(insulin)Tj
2.982 0 Td
(and)Tj
1.7348 0 Td
(all)Tj
1.1452 0 Td
(GTT)Tj
2.16 0 Td
(data)Tj
1.9105 0 Td
(were)Tj
2.126 0 Td
(analysed)Tj
3.6453 0 Td
(using)Tj
2.3925 0 Td
(two-way)Tj
-32.7456 -1.2983 Td
(analysis)Tj
3.3278 0 Td
(of)Tj
1.0148 0 Td
(variance)Tj
3.5716 0 Td
(\(ANOVA\))Tj
4.4504 0 Td
(followed)Tj
3.6453 0 Td
(by)Tj
1.1849 0 Td
(the)Tj
1.4683 0 Td
(student-Newman-Keuls)Tj
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9.7852 0 Td
[()4()7()9( \n)6()4()]TJ
/F7 1 Tf
3.4639 0 Td
(test.)Tj
1.8255 0 Td
(Cumula-)Tj
-33.7377 -1.3039 Td
(tive)Tj
1.661 0 Td
(food)Tj
2.0523 0 Td
(intake)Tj
2.6872 0 Td
(was)Tj
1.7008 0 Td
(analysed)Tj
3.6453 0 Td
(using)Tj
2.3925 0 Td
(Student's)Tj
3.8948 0 Td
(t-test.)Tj
2.4774 0 Td
(Area)Tj
2.1317 0 Td
(under)Tj
2.6192 0 Td
(the)Tj
1.4683 0 Td
(curve)Tj
2.4208 0 Td
(\(AUC\))Tj
2.982 0 Td
(was)Tj
1.7008 0 Td
(calcu-)Tj
-33.8341 -1.2983 Td
(lated)Tj
2.1486 0 Td
(using)Tj
2.3868 0 Td
(trapezoidal)Tj
4.6601 0 Td
(rule)Tj
1.7915 0 Td
(with)Tj
1.9955 0 Td
(baseline)Tj
3.4299 0 Td
(correction.)Tj
4.5865 0 Td
(All)Tj
1.4003 0 Td
(other)Tj
2.3471 0 Td
(data)Tj
1.9105 0 Td
(including)Tj
4.0422 0 Td
(AUC)Tj
2.3074 0 Td
(were)Tj
-33.0064 -1.2982 Td
(analysed)Tj
3.651 0 Td
(using)Tj
2.3867 0 Td
(one-way)Tj
3.6227 0 Td
(ANOVA.)Tj
3.9911 0 Td
(p)Tj
/F12 1 Tf
0 Tc
(<)Tj
/F7 1 Tf
-0.004 Tc
(0.05)Tj
3.1635 0 Td
(was)Tj
1.6951 0 Td
(considered)Tj
4.6034 0 Td
(to)Tj
1.0261 0 Td
(be)Tj
1.1509 0 Td
(statistically)Tj
4.6091 0 Td
(significant.)Tj
ET
Q
q
1 j
1 J
0 w
11.9999 0 0 11.9999 200.0125 456.3779 cm
BT
/F2 1 Tf
1 TL
-0.0033 Tc
0 0 Td
(3.)Tj
1.0441 0 Td
(Results)Tj
/F11 1 Tf
-1.0441 -1.5023 Td
(3.1.)Tj
1.7055 0 Td
(Chronic)Tj
3.6284 0 Td
(administration)Tj
6.5008 0 Td
(of)Tj
1.0677 0 Td
(acylated)Tj
3.6378 0 Td
(apelin-13)Tj
4.1245 0 Td
(amide)Tj
2.7969 0 Td
(analogues)Tj
-23.4616 -1.167 Td
(improves)Tj
4.096 0 Td
(metabolic)Tj
4.3324 0 Td
(status)Tj
2.674 0 Td
(in)Tj
1.0677 0 Td
(high-fat)Tj
3.567 0 Td
(fed)Tj
1.5307 0 Td
(mice)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 200.0125 407.3385 cm
BT
/F7 1 Tf
1 TL
-0.004 Tc
0 0 Td
(A)Tj
0.9014 0 Td
(significant)Tj
4.388 0 Td
(decrease)Tj
3.6113 0 Td
(in)Tj
1.0318 0 Td
(%)Tj
0.9808 0 Td
(bodyweight)Tj
4.8812 0 Td
(change)Tj
3.0444 0 Td
(was)Tj
1.6951 0 Td
(noted)Tj
2.5285 0 Td
(with)Tj
1.9956 0 Td
(all)Tj
1.1451 0 Td
(treatment)Tj
4.1386 0 Td
(groups)Tj
2.965 0 Td
(compared)Tj
-33.3068 -1.2982 Td
(to)Tj
1.0261 0 Td
(lean)Tj
1.8708 0 Td
(and)Tj
1.7292 0 Td
(high-fat)Tj
3.3788 0 Td
(fed)Tj
1.457 0 Td
(saline)Tj
2.5002 0 Td
(treated)Tj
2.999 0 Td
(mice)Tj
2.1543 0 Td
(\(p)Tj
/F12 1 Tf
0 Tc
(<)Tj
/F7 1 Tf
-0.004 Tc
(0.01)Tj
3.498 0 Td
(and)Tj
1.7348 0 Td
(p)Tj
/F12 1 Tf
0 Tc
(<)Tj
/F7 1 Tf
-0.004 Tc
(0.001;)Tj
0.83 0.64 0.02 0 k
3.8607 0 Td
(Fig)Tj
1.4797 0 Td
(1A)Tj
1.3776 0 Td
(and)Tj
1.7348 0 Td
(1B)Tj
0 g
(\).)Tj
1.8369 0 Td
(Cumulative)Tj
-32.6379 -1.2983 Td
(energy)Tj
2.9083 0 Td
(intake)Tj
2.6872 0 Td
(was)Tj
1.6951 0 Td
(also)Tj
1.7688 0 Td
(significantly)Tj
5.091 0 Td
(decreased)Tj
4.1329 0 Td
(in)Tj
1.0375 0 Td
(apelin)Tj
2.6589 0 Td
(treated)Tj
2.9933 0 Td
(mice)Tj
2.1543 0 Td
(\(27%)Tj
2.2677 0 Td
(decrease,)Tj
3.8325 0 Td
(P)Tj
/F12 1 Tf
0 Tc
(<)Tj
/F7 1 Tf
-0.004 Tc
(0.01;)Tj
0.83 0.64 0.02 0 k
-33.2275 -1.3039 Td
(Fig)Tj
1.474 0 Td
(1C)Tj
0 g
(\).)Tj
1.9162 0 Td
(Both)Tj
2.1316 0 Td
(acylated)Tj
3.4526 0 Td
(apelin-13)Tj
3.9571 0 Td
(amide)Tj
2.6872 0 Td
(analogues)Tj
4.1613 0 Td
(significantly)Tj
5.0853 0 Td
(decreased)Tj
4.1272 0 Td
(non-fasted)Tj
4.5014 0 Td
(blood)Tj
2.5115 0 Td
(glu-)Tj
-36.0054 -1.2983 Td
(cose)Tj
1.9332 0 Td
(\(P)Tj
/F12 1 Tf
0 Tc
(<)Tj
/F7 1 Tf
-0.004 Tc
(0.05)Tj
3.5433 0 Td
(and)Tj
1.7291 0 Td
(P)Tj
/F12 1 Tf
0 Tc
(<)Tj
/F7 1 Tf
-0.004 Tc
(0.01;)Tj
0.83 0.64 0.02 0 k
3.4299 0 Td
(Fig)Tj
1.4796 0 Td
(1D)Tj
0 g
(\))Tj
1.7745 0 Td
(and)Tj
1.7291 0 Td
(increased)Tj
3.9969 0 Td
(non-fasting)Tj
4.8358 0 Td
(plasma)Tj
3.0331 0 Td
(insulin)Tj
2.9877 0 Td
(\(P)Tj
/F12 1 Tf
0 Tc
(<)Tj
/F7 1 Tf
-0.004 Tc
(0.05)Tj
3.5433 0 Td
(and)Tj
-34.0155 -1.2982 Td
(P)Tj
/F12 1 Tf
0 Tc
(<)Tj
/F7 1 Tf
-0.004 Tc
(0.01;)Tj
0.83 0.64 0.02 0 k
3.4242 0 Td
(Fig)Tj
1.4853 0 Td
(1E)Tj
0 g
(\).)Tj
1.8255 0 Td
(Liraglutide)Tj
4.5865 0 Td
(evoked)Tj
3.0557 0 Td
(similar)Tj
2.9877 0 Td
(effects)Tj
2.7212 0 Td
(although,)Tj
3.9798 0 Td
(with)Tj
2.0013 0 Td
(the)Tj
1.4683 0 Td
(exception)Tj
4.0932 0 Td
(of)Tj
1.0148 0 Td
(plasma)Tj
-32.6435 -1.3039 Td
(insulin,)Tj
3.2087 0 Td
(with)Tj
2.0013 0 Td
(latter)Tj
2.2904 0 Td
(onset)Tj
2.3584 0 Td
(or)Tj
1.0998 0 Td
(less)Tj
1.6101 0 Td
(durability.)Tj
ET
Q
q
1 j
1 J
0 w
11.9999 0 0 11.9999 200.0125 295.9937 cm
BT
/F11 1 Tf
1 TL
-0.0033 Tc
0 0 Td
(3.2.)Tj
1.7055 0 Td
(Chronic)Tj
3.6284 0 Td
(administration)Tj
6.5008 0 Td
(of)Tj
1.0677 0 Td
(acylated)Tj
3.6378 0 Td
(apelin-13)Tj
4.1245 0 Td
(amide)Tj
2.7969 0 Td
(analogues)Tj
4.3512 0 Td
(reduces)Tj
-27.8128 -1.1669 Td
(glycemic)Tj
3.8551 0 Td
(excursion)Tj
4.2473 0 Td
(in)Tj
1.0677 0 Td
(high-fat)Tj
3.567 0 Td
(fed)Tj
1.5307 0 Td
(mice)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 200.0125 264.9826 cm
BT
/F7 1 Tf
1 TL
-0.004 Tc
0 0 Td
(Administration)Tj
6.4175 0 Td
(of)Tj
1.0148 0 Td
(acylated)Tj
3.464 0 Td
(apelin-13)Tj
3.9571 0 Td
(amide)Tj
2.6929 0 Td
(analogues)Tj
4.1669 0 Td
(or)Tj
1.0998 0 Td
(liraglutide)Tj
4.2917 0 Td
(for)Tj
1.3889 0 Td
(28)Tj
1.1679 0 Td
(days,)Tj
2.2223 0 Td
(significantly)Tj
-31.8838 -1.2982 Td
(reduced)Tj
3.4412 0 Td
(glycemic)Tj
3.7474 0 Td
(excursion)Tj
4.1158 0 Td
(after)Tj
2.0353 0 Td
(an)Tj
1.2019 0 Td
(intraperitoneal)Tj
6.1738 0 Td
(or)Tj
1.0998 0 Td
(oral)Tj
1.7745 0 Td
(glucose)Tj
3.1748 0 Td
(load)Tj
1.9389 0 Td
(\(P)Tj
/F12 1 Tf
0 Tc
(<)Tj
/F7 1 Tf
-0.004 Tc
(0.05)Tj
3.5433 0 Td
(to)Tj
1.0204 0 Td
(P)Tj
/F12 1 Tf
0 Tc
(<)Tj
/F7 1 Tf
-0.004 Tc
(0.001;)Tj
0.83 0.64 0.02 0 k
-33.2671 -1.2983 Td
(Fig)Tj
1.4796 0 Td
(2A,)Tj
1.6044 0 Td
(2C,)Tj
1.5817 0 Td
(2E)Tj
1.27 0 Td
(and)Tj
1.7291 0 Td
(2F)Tj
0 g
(\))Tj
1.5647 0 Td
(and)Tj
1.7291 0 Td
(post)Tj
1.9049 0 Td
(oral)Tj
1.7745 0 Td
(glucose)Tj
3.1748 0 Td
(load)Tj
1.9332 0 Td
(\(P)Tj
/F12 1 Tf
0 Tc
(<)Tj
/F7 1 Tf
-0.004 Tc
(0.05)Tj
3.5433 0 Td
(to)Tj
1.0261 0 Td
(P)Tj
/F12 1 Tf
0 Tc
(<)Tj
/F7 1 Tf
-0.004 Tc
(0.001;)Tj
0.83 0.64 0.02 0 k
3.9061 0 Td
(Fig)Tj
1.4797 0 Td
(2E)Tj
1.2642 0 Td
(and)Tj
1.7291 0 Td
(2F)Tj
0 g
(\).)Tj
1.7915 0 Td
(pGlu)Tj
-34.486 -1.3039 Td
(\(Lys)Tj
ET
Q
q
1 j
1 J
0 w
7.4999 0 0 6.6659 216.9637 230.4566 cm
BT
/F7 1 Tf
1 TL
-0.0053 Tc
0 0 Td
(8)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 220.4787 225.9779 cm
BT
/F7 1 Tf
1 TL
-0.004 Tc
0 0 Td
(GluPAL\)apelin-13)Tj
7.5627 0 Td
(amide)Tj
2.6816 0 Td
(was)Tj
1.6894 0 Td
(the)Tj
1.4627 0 Td
(most)Tj
2.194 0 Td
(effective)Tj
3.4979 0 Td
(as)Tj
1.0092 0 Td
(treated)Tj
2.9877 0 Td
(mice)Tj
2.1429 0 Td
(showed)Tj
3.2429 0 Td
(no)Tj
1.2642 0 Td
(significant)Tj
4.3767 0 Td
(dif-)Tj
-36.1585 -1.2982 Td
(ference)Tj
3.118 0 Td
(in)Tj
1.0375 0 Td
(overall)Tj
2.9027 0 Td
(glucose)Tj
3.1748 0 Td
(excursion)Tj
4.1158 0 Td
(compared)Tj
4.2406 0 Td
(to)Tj
1.0262 0 Td
(lean)Tj
1.8765 0 Td
(control)Tj
3.1181 0 Td
(mice)Tj
2.1543 0 Td
(\()Tj
0.83 0.64 0.02 0 k
(Fig)Tj
1.8198 0 Td
(2B)Tj
0 g
(\).)Tj
1.8425 0 Td
(The)Tj
1.7802 0 Td
(peptide)Tj
3.1975 0 Td
(treat-)Tj
-35.4045 -1.2983 Td
(ments)Tj
2.6702 0 Td
(also)Tj
1.7688 0 Td
(significantly)Tj
5.0853 0 Td
(increased)Tj
4.0025 0 Td
(the)Tj
1.4683 0 Td
(overall)Tj
2.9027 0 Td
(plasma)Tj
3.033 0 Td
(insulin)Tj
2.9877 0 Td
(response)Tj
3.7304 0 Td
(after)Tj
2.0353 0 Td
(intraperitoneal)Tj
-29.6842 -1.3039 Td
(\(P)Tj
/F12 1 Tf
0 Tc
(<)Tj
/F7 1 Tf
-0.004 Tc
(0.01)Tj
3.5432 0 Td
(and)Tj
1.7292 0 Td
(P)Tj
/F12 1 Tf
0 Tc
(<)Tj
/F7 1 Tf
-0.004 Tc
(0.001;)Tj
0.83 0.64 0.02 0 k
3.9061 0 Td
(Fig)Tj
1.4796 0 Td
(2C)Tj
1.355 0 Td
(and)Tj
1.7291 0 Td
(2D)Tj
0 g
(\))Tj
1.7745 0 Td
(or)Tj
1.0998 0 Td
(oral)Tj
1.7745 0 Td
(glucose)Tj
3.1748 0 Td
(load)Tj
1.9389 0 Td
(\(P)Tj
/F12 1 Tf
0 Tc
(<)Tj
/F7 1 Tf
-0.004 Tc
(0.05)Tj
3.5433 0 Td
(and)Tj
1.7291 0 Td
(P)Tj
/F12 1 Tf
0 Tc
(<)Tj
/F7 1 Tf
-0.004 Tc
(0.01;)Tj
0.83 0.64 0.02 0 k
3.4242 0 Td
(Fig)Tj
1.4797 0 Td
(2G)Tj
1.4116 0 Td
(and)Tj
-35.0926 -1.2983 Td
(2H)Tj
0 g
(\).)Tj
2.0296 0 Td
(The)Tj
1.7801 0 Td
(insulinotropic)Tj
5.879 0 Td
(responses)Tj
4.0932 0 Td
(were)Tj
2.1203 0 Td
(much)Tj
2.5228 0 Td
(greater)Tj
3.0047 0 Td
(than)Tj
2.0296 0 Td
(in)Tj
1.0375 0 Td
(mice)Tj
2.1487 0 Td
(fed)Tj
1.4626 0 Td
(on)Tj
1.2756 0 Td
(a)Tj
0.652 0 Td
(normal)Tj
3.1464 0 Td
(diet)Tj
-33.1821 -1.2982 Td
(\(P)Tj
/F12 1 Tf
0 Tc
(<)Tj
/F7 1 Tf
-0.004 Tc
(0.001,)Tj
0.83 0.64 0.02 0 k
4.2406 0 Td
(Fig)Tj
1.4796 0 Td
(2D)Tj
1.4343 0 Td
(and)Tj
1.7292 0 Td
(2H)Tj
0 g
(\).)Tj
2.0296 0 Td
(Similarly,)Tj
4.0251 0 Td
(both)Tj
2.0636 0 Td
(acylated)Tj
3.4583 0 Td
(apelin-13)Tj
3.9628 0 Td
(amide)Tj
2.6872 0 Td
(analogues)Tj
4.1669 0 Td
(and)Tj
1.7348 0 Td
(liraglutide)Tj
-33.012 -1.2983 Td
(significantly)Tj
5.0853 0 Td
(reduced)Tj
3.4469 0 Td
(the)Tj
1.4683 0 Td
(blood)Tj
2.5172 0 Td
(glucose)Tj
3.1747 0 Td
(excursion)Tj
4.1159 0 Td
(after)Tj
2.0353 0 Td
(15)Tj
1.1679 0 Td
(min)Tj
1.8538 0 Td
(feeding)Tj
3.1634 0 Td
(\(P)Tj
/F12 1 Tf
0 Tc
(<)Tj
/F7 1 Tf
-0.004 Tc
(0.05)Tj
3.5433 0 Td
(and)Tj
1.7348 0 Td
(P)Tj
/F12 1 Tf
0 Tc
(<)Tj
/F7 1 Tf
-0.004 Tc
(0.01;)Tj
0.83 0.64 0.02 0 k
-33.3068 -1.3039 Td
(Fig)Tj
1.4797 0 Td
(3A)Tj
0 g
(\).)Tj
1.9445 0 Td
(The)Tj
1.7801 0 Td
(two)Tj
1.7121 0 Td
(acylated)Tj
3.464 0 Td
(apelin-13)Tj
3.9571 0 Td
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