1 : ( ) (0 1- PJ4- PG4-0 1VN02-0055) ( ) : ( ) :De ve lo pme nt of the functio na l food for tre atme nt of diabe te s me llitus with a new me cha nis m of actio n : () :
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3 :. ( ) ( )Development of the functional food for treatment of diabetes mellitus with a new mechanism of action. 1. - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - 1 2. - - - - - - - - - - - - - - - - - - - - - - - - - - - - 3 3. - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - 186 4. - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - 187 5. - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - 188 6. - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - 189 7. - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - 190
4 : ( ),, () () 2001420025 2 ob/ ob m ou se db/ db m ou se INM 803glu cose in sulin toleran ce,. leptin m ou seob/ ob m ou se db/ db m ou seinm80380% eth anol ex tract 9 0.05%, 0.1%, 0.2%on e- w ay ANOVA test. ob/ ob m ou se INM 803 0.05% 0.1% 0.2%6 (P < 0.05). 6(P < 0.05) 0.2%. plasm a in sulin 3(p< 0.05). db/ db m ou se INM 803 0.05% 0.1% 0.2%,. in sulin toleran ce testglucose tolerance test. INM 803 3690.1% 0.2%.(p < 0.05) INM 803 INM 803 2000 m g/ kg14.. INM 803 2000 m g/ kg. INM 803.
5 : ( ) Project S ummery,, 2. Development of the functional food for treatment of diabetes mellitus with a new T it le mechanism of action K ey W ords treatment of diabetes mellitus, functional food, a new mechanism of action In s tit ut e Biosyn ergen Inc. P roj e ct L e ader Don g - keun,song A s s o ci at e d Com pan y P roj e ct P eri od 2001. 4. 2002. 5. Biosynerg en In c. T o dev elop an effectiv e and safe food/ dru g for reducing high blood su gar, w e studied th e effect of INM - 803 in blood sug ar redu cin g effect, in sulin tolerance, an d acute tox icity u sing type 2 diab etes anim al m odels, ob/ ob m ou se and db/ db mou se. INM - 803 (80% eth anol ex tract ; 0.05%, 0.1%, 0.2% ) w as administered orally for 9 w eek s to ob/ ob m ou se, w hich lack s leptin. INM 803 (0.05% 0.1% 0.2% ) decr eased blood su gar lev els fr om 6 w eek of administration in ob/ ob m ou se. Plasm a in sulin lev els sh ow ed a significant decrease (p< 0.05) fr om 6 w eek of adm inistr ation. INM 803 (0.05% 0.1% 0.2% ) also decreased blood su gar lev els in db/ db m ou se w ith out chan ges in body w eight. Interestingly, the INM803- induced decrease in blood su gar lev els w a s maintained up to 9 w eek s after discontinuation of INM - 803 (p< 0.05). T o study th e acute toxicity of INM - 803, INM - 803 w as administered in a sin gle oral dose of 2000 m g/ kg. And anim als w ere ob serv ed for toxic symptom s for 14 day s in m ale an d female rats. N o tox ic clinical m anifestation s w ere ob serv ed inclu ding lethality. No path ological findin g s w ere ob serv ed in autopsy. T he lethal dose of INM - 803 is con sidered to be ab ov e 2000 m g/ kg. In conclu sion, it is su gg est ed that ILM - 803 can be a v ery effectiv e in corr ection of high blood su gar w ith a good safety pr ofile.
6 : 1. 1. 20 1, 15, 105. 2030 3 (Harris, 1998). 1 2-4, (blindness)., 400., 8%- 10%.,.. 90%- 95% 2. 2 db/ db mouse INM803 INM803 INM803, NM803 9, INM803.,,. INM803,. INM803,,. INM803 (BS219), INM803 BS219.
INM803. INM803 INM803BS219 INM803 BS219 INM803 BS219 INM803,. 1. INM8032db/ db ob/ ob, 1streptozotocin.. 2. INM803 BS2192db/ db ob/ ob, 1streptozotocin.. 3. INM803glu cose toleran ce test in sulin tolerance test,, cdna array. glucose tran sporterglut 4, IRS 1-4 (in sulin receptor sub strate) (immun ohistochemistry ). 4. INM803 BS219glu cose toleran ce test in sulin tolerance test,, cdna array. glu cose tran sporter GLUT 4, IRS 1-4 (in sulin receptor sub strate ) (immun ohistochemistry ) (in situ hybridization, RT - PCR, N orthern blot, w estern blot ). 5. INM803 BS219( ), ( ) 4, (3 ) 6. INM80390%-,. (10 kg). ( 1 )
7. BS219BS 219 chir al sy nth ondiol. (2 ) 2. 1) INM8032ob/ ob INM803 (0.05%, 0.1%, 0.2% ) INM803,, (1) ob/ ob 8(0 time) 230 mg/ dl17(9). INM803INM803 (0.05%, 0.1%, 0.2% ) INM80360.05% (p < 0.001), 0.1% (p < 0.001), 0.2% (p < 0.001)(Fig 1 ) (2) ob/ ob 8(0 time) 25 g17(9) 46g. INM803INM803 0.2% (p< 0.05) (F ig 2 ) (3) ob/ ob 8(0 time) 5 ng/ dl mouse 10 17(9). INM803 INM803 (0.05%, 0.1%, 0.2% )INM803 30.2% (p< 0.05) 9INM803 (0.05%, 0.1%, 0.2% ) (F ig3 ) 2 ) INM8032db/ db INM803 (0.05%, 0.1%, 0.2% ),,, (1) db/ db 8(0 time) 100 mg/ dl 17(9) 500 mg/ dl. INM803 INM803 (0.05%, 0.1%, 0.2% )INM803 90.05% (p < 0.05), 0.1% (p< 0.01), 0.2% (p< 0.01) (F ig4 ) (2) db/ db 8(0 time) 30 g17(9)
(3) ob/ ob 8(0 time) 10 ng/ dl mouse 10 7ng/ 17(9). INM803INM803 (0.05%, 0.1%, 0.2% ) INM803.(Fig 6) (4) INM803glucose 2db/ db INM803 (0.05%, 0.1%, 0.2% )9 db/ db m ou se 12glu cose (2g/ kg ) 30. (Fig 7) (5) INM803 2db/ db INM803 (0.05%, 0.1%, 0.2% )9 db/ db m ou se 12in sulin (0.5 unit/ kg ) 30 INM803 0.1% (p < 0.01), 0.2% (p< 0.05). (Fig 8) 3 ) INM803 2db/ db INM803 (0.05%, 0.1%, 0.2% )9 INM 803 9, 9INM803 0.05% (p< 0.01), 0.1% (p < 0.01), 0.2% (p < 0.001) (Fig 9) 4 ) 1 streptozotocin streptozotocin (250 m g/ kg ) 1 300 m g/ dl mou se INM803 (0.05%, 0.1%, 0.2% )9 (Fig 10) 5) BS2192db/ db INM803 (0.002%, 0.01%, 0.03% ), (1) db/ db 8(0 time) 200 mg/ dl 17(9). INM803BS219 (0.05%, 0.1%, 0.2% ) INM803(F ig 11) (2) INM803BS219 (0.05%, 0.1%, 0.2% )INM803 (Fig 12) 6) INM803 2,000mg/ kg 14. (1)
7) 2 INM 803 1,600mg/ kg 1,600mg 800 mg/ kg. (2 ) 8) Chinese Hamster Lung (CHL) INM 803 CHL. ( 3 )
Fig. 1. ob/ ob mouse INM 803. ob/ ob mouseinm 8030, 0.05 %, 0.1 %, 0.2 % 3. * P<0.05, *** P<0.001 (n=6)
Fig. 2. ob/ ob mouse INM 803. ob/ ob mouseinm 8030, 0.05 %, 0.1 %, 0.2 % 3. * P<0.05 (n=6)
Fig. 3. ob/ ob mouse INM 803. ob/ ob mouseinm 8030, 0.05 %, 0.1 %, 0.2 % 3 enzyme- immunoassay. * P<0.05, ** P< 0.01 (n=6)
Fig. 4. db/ db mouse INM 803. db/ db mouseinm 8030, 0.05 %, 0.1 %, 0.2 % 3. * P<0.05, ** P<0.01 (n =6)
Fig. 5. db/ db mouse INM 803. db/ db mouseinm 8030, 0.05 %, 0.1 %, 0.2 % 3.
Fig. 6. db/ db mouse INM 803. db/ db mouseinm 8030, 0.05 %, 0.1 %, 0.2 % 3 enzyme- immunoassay.
Fig. 7. INM803glucose 2db/ db INM803 (0.05%, 0.1%, 0.2% )9 db/ db mou se 12 glucose (2g/ k g ) 30. (n =6)
Fig. 8. INM803 2db/ db INM803 (0.05%, 0.1%, 0.2% )9 db/ db mou se 12 in sulin (0.5 unit/ kg ) 30. * P<0.05, ** P<0.01 (n =6)
Fig. 9. INM803 2db/ db INM803 (0.05%, 0.1%, 0.2% )9 INM 803 3. ** P<0.01, *** P<0.001 (n =6)
Fig. 10. 1streptozotocin streptozotocin 250 m g/ k g 1 300 m g/ dl m ou se INM803 0.05%, 0.1%, 0.2%9.
Fig. 11. db/ db mouse INM 219. db/ db mouseinm 2190, 0.002 %, 0.01 %, 0.03 % 3.
Fig. 12. db/ db mouse INM 219. db/ db mouseinm 2190, 0.002 %, 0.01 %, 0.03 % 3.
3.. 5% 90% 2( ) 1,600 14. 2 db/ db mouse INM803. INM803, NM803 9. INM803.,. INM803 INM803 2,000mg/ kg 14,. 2 INM 803 1,600mg/ kg 1,600mg 800 mg/ kg, Chinese Hamster Lung (CHL) INM 803CHL. INM803.
4. 1 (: ) 3 2 (: ) 3 (: ) 4 (: ) 3 (1) SCI (Impact Factor ) SCI (2) (3 ) (4 ) 1)(),,, 2002-1508, 2002. 01. 10. 2)(),,, 40-2001- 0027457, 2001.06.25 3)(), Glu care,, 40-2001- 0030939, 2001.07.13 (5 )
(6 ).. INM803 db/ db mou se, ob/ ob m ou se, streptozotocin m ou se 60.1% INM803 glucose tolerance test in sulin toleran ce test glucose in sulin. B S219 BS 219. INM803( ), ( ) 4, INM803 2,000mg/ kg 14, 2 INM 803 1,600mg/ kg 1,600mg 800 mg/ kg Chinese Hamster Lung (CHL) INM 803CHL. 5. (1) 2 1 Dia b et e s (IF :9.0 19) 1 0 (2) db/ db mouse, ob/ ob mouse ( ).
2003. 6. 1)Kee- W on Kim, H ee- Doo Kim, Jun - Sub Jung, Ran - Sook W oo, H ee- Sun g Kim, H ong - W on Suh, Yung - Hi Kim, Don g - Keun Song : Ch aracterization of antidepressant - like effect s of p - syn ephrine stereoisom er s. Naunyn - Schmiedeberg ' s Archiv es of Pharm acology 364:21-26, 2001. 2)Son g, Don g K., Suh, H ong W., Jun g Jun S., Son, Kun H.,W ie Myung B. an d Kim, Yun g Hi.: Antidepressant - lik e effects of p - synephrin e in m ou se m odels of imm obility tests. Neuroscience Letter s. 214:107-110, 1996. 3) Berthiaume N, Zinker BA. :Metabolic responses in a model of insulin resistance: Comparison between oral glucose and meal tolerance tests. Metabolism. 51(5):595-8, 2002 4) Gueorguiev M, Goth ML, Korbonit s M. Leptin and puberty : a review. Pituitary. Jan - Apr ;4(1-2):79-86, 2001 5) Rosenbaum M, Nicolson M, Hir sch J, Murphy E, Chu F, Leibel RL : Effect s of w eight ch ang e on plasm a leptin concentr ation s an d energy expenditure. J Clin E ndocrinol M etab82 : 3647-3654,1997 6) Saladin R, De Vos P, Guerre- Millo M, Leturque A, Girard J, Staels B, Au w erx J : T ran sient in crease in ob ese gene ex pression after food intake or in sulin administration. N ature377 : 527-529,1995 7)Pelleym ounter MA, Cullen MJ, Baker MB, H echt R, W inter s D, Boone T, Collin s F : Effect s of th e obese gene produ ct on b ody w eight regulation in ob/ ob mice. S cience269 : 540-543,1995 8) Cohen B, Novick D, Rubinstein M : M odulation of insulin activities by leptin. S cience 274:1185-1188, 1996 9) Kam ohara S, Burcelin R, H alaa s JL, Friedman JM, Ch arron MJ : A cute stimulation of glu cose m etabolism in mice by leptin treatment. N ature 389:374-377, 1997 10) Colem an DL Effects of parabiosis of obese w ith diabetes and norm al mice. Diabetologia 9:294298, 1973 11) Pelleym ounter MA, Cullen MJ, Baker MB, Hecht R, W inter s D, Boon e T, Collin s F Effect s of th e obese gene pr odu ct on b ody w eight regulation in ob/ ob mice. S cien ce 269:540543, 1995
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