 
   Ranirestat Improved Nerve Conduction
Velocities, Sensory Perception, andIntraepidermal Nerve Density in Rats with
Overt Diabetic Polyneuropathy.
-,.()*+#-*+"   !&  %$ ' &$• ! "' (DPN);>@
3*( :)-! 6,A+• &' =#9>AQOLC0<.*% EKNI:LGF6,A17/2B5-A+• 3.38/?*DPN: 9DJMOH4A
;2B5-8-+• DPN,-,.)+ *0/(
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NADPH/3#+6'(3.+63NAD+NADP+NADH(3.+63↑NADPH↓

↑1"!-&+63↓$3)*"5↓

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↑!
• EKHLG)*+ #MARIN<,IJFLK
% &;'*7.BEKHLG)*MAR)D845#7.B• ARI:?BDPN;(1)2
3C60
A, epalrestat;=2"3C6/B• 414,epalrestat<(45DPN: 46<92$>@C6/9/-

1NHotta.N. Diabetes Care. 2006 Jul;29(7):1538-44.

•%ARI")ranirestat&'( $AR+DPN0-1$!%,1/.21+ $ )# *!)2) 23Ota AJ Diabetes Res. 2013;2013:175901.

• ranirestat2 31."1 ! / 19 4+ 3,4)()8-&7%• ;#.5 ! 9*+($102 4680',+5:%3) Bril V. Diabetes Care. 2004 Oct;27(10):2369-75. 4) Satoh JJ Diabetes Res. 2016;2016:5383797
5) Sekiguchi K. J Diabetes investig. 2019; 10:466-474

• 534,"!).ranirestat-DPN--6,7)&2)!1 '#'*.
 #/ranirestat$ &2)"0
DPN -.&2)!+!
• ranirestat-DPN,"%1-+,(!).+.&2)!+!

6) Matsumoto T. J Pharmacol Sci. 2008 Jul;107(3):231-7. 7) Matsumoto T J Pharmacol Sci. 2008 Jul;107(3):340-8.

"STZ  84;:35-'(/)+DPN-*/ranirestat. 0*/%#712 (DRG)-*/69><=.
!0&,$ranirestat. -*/ 0*/%

41V
• 4/53SD rat (Non-DM: $ n=10, NP
IO$n=10; DM: $ n=9, NPIO$ n=8)
@ 9HMQNMJMGRF&%96U/0
@2' 300mg/dL(16.7mM)>?+7•12/CD6ranirestat 1mg/kgF6/0!:E7• DPNB6! .6-A*1(NPRKSLHMT6)!#" F8=,
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Nondiabetic rats
PreTreatment

Diabetic rats

Post Treatment
Placebo

Rani
8PreTreatment

Post Treatment
PlaceboRani

57

Number

19-20

4-6

 (mM)

6.71.3

16.84.6†

13.22.9† 28.33.9* 29.64.9* 30.54.1*(g)

518325663548596

1625454*

24134*

Result are means SD.
*: p < 0.05 versus pre-treatment nondiabetic rats and †: p < 0.05 versus pre- treatment nondiabetic rats.

25367*1  
Ranirestat

(m/s)



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70
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70
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6060

*

50

40

30

30

2020DM†*5040N*NDM
placebo

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12 w: 12 weeks after induction of diabetes, 18 w: 18 weeks after induction of diabetes,
N: non-diabetic rats, DM: diabetic rats *: p < 0.05 compared with N or N-placebo, †: p < 0.05 compared with D-placebo.
n = 15 ~ 18 at 12 w, n = 8 ~ 10 in groups treated with placebo or ranirestat, n = 3 in D-epa. Bold horizontal line in each group demonstrates an average value.

1  
Ranirestat70

70
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treatment

60

60

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20



(m/s)

(m/s)

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NDMraniDMepa12 w: 12 weeks after induction of diabetes, 18 w: 18 weeks after induction of diabetes,
N: non-diabetic rats, DM: diabetic rats *: p < 0.05 compared with N or N-placebo, †: p < 0.05 compared with DM-placebo.
n = 15 ~ 18 at 12 w, n = 8 ~ 10 in groups treated with placebo or ranirestat, n = 3 in D-epa. Bold horizontal line in each group demonstrates an average value.

1#!"Ranirestat!"(s) 25 

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*
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N: non-diabetic rats, DMdiabetic rats, rani: rats treated with ranirestat, epa: rats treated with epalrestat. *: p < 0.05 compared with N or non-diabetic placebo, ##: p <0.005 compared with diabetic placebo. n = 15 ~ 18 at 12 w, n = 8 ~ 10 in groups treated with placebo or ranirestat, n = 3 in rats treated with epalrestat. Bold
horizontal line in each group demonstrates an average value.

$;#< !

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45
40
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25DMrani

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15
10placeboraniN
N: non-diabetic rats, DM: diabetic rats, placebo: rats treated with placebo, rani: rats treated with ranirestat.
*: p < 0.05 versus N treated with placebo, †: p < 0.05 versus D treated with ranirestat, n = 6–8 in each group. Scale bar: 50 µm.

placebo
DMrani02R
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200μm

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2000

2500
2000

1500

1500

1000

1000
500

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rani

ctrl: control medium, rani: medium supplemented with 1 µmol/l ranirestat. *p<0.05 versus ctrl. n=10 in each group.

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8EE Schartner. Experimantal Neurology . 2018 vol.309:134-147.

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