< D C0D3BCF8BCBA2E666D>

Size: px

Start display at page:

Download "< D C0D3BCF8BCBA2E666D>"

현준 내
6 years ago
Views:

1 w z Kor. J. Pharmacogn. 40(3) : 196 Ê 204 (2009) 생약복합제의 Streptozotocin 유발당뇨및대사성증후군모델동물에서의혈당에미치는효과 w 1 Á 2 Á 1 Á½ ³ 3 Á 4 Á½x 5 Á z 5 Á 5 Á» 5 Á 1,2,3 * 1 w w t w, 2 w w t z sƒ» l (RIC), 3 w w, 4 w w w, 5 Effects of Herbal Complex on Blood Glucose in Streptozotocin-induced Diabetic Rats and in Mice Model of Metabolic Syndrome Han-Seok Park 1, Yeon Sil Lee 2, Se-Jin Choi 1, Jin-Kyu Kim 3, Yun-Lyul Lee 4, Hyun Gwen Kim 5, Sam Hoi Koo 5, Dae Hoy Ku 5, Seung Il Ki 5 and Soon Sung Lim 1,2,3 * 1 Department of Food and Nutrition, Hallym University, Chuncheon, , Korea 2 Center for Efficacy Assessment and Development of Functional Foods and Drugs, Hallym University, Chuncheon, , Korea 3 Institute of Natural Medicine, Hallym University, Chuncheon, , Korea 4 Department of Physiology, Hallym University, Chuncheon, , Korea 5 C-Med Co., Wonju, , Korea Abstract This study was carried out to investigate the in vivo and in vitro inhibitory effect of a traditional herbal complex (HC) extract prepared from a mixture of four oriental herbs (Dioscorea Rhizoma, Glycine soja Sieb. et Zucc, Bombycis corpus, Fermented Glycine soja) that have been widely used for the treatment and prevention of diabetes mellitus on hyperglycemia. The water extract of HC showed potent inhibitory effect on α-glucosidase with IC 50 value of 1.24 mg/ml. Additionally, the ethanol extract of HC was also found to exhibit significant inhibitory effect against protein tyrosine phosphatase 1β (PTP1β), which is known as a major regulator of both insulin and leptin signaling. In the PTP1β inhibitory assay, the most active n-hexane fraction obtained from the ethanol extract of HC, was identified as a mixture of fatty acid derivatives by gas chromatography mass spectrometry (GC-MS). In high-fat diet-low dose streptozotocin (STZ)-induced diabetic rat, the water extract of HC improved the oral glucose intolerance as compared with rosiglitazone. HC also caused a marked decrease of body weight and fasting blood glucose and a significant improvement on glucose tolerance in metabolic syndrome mice model. These findings support that this traditional HC may be useful in the control of blood glucose in diabetes mellitus and metabolic syndrome. Key words Herbal Complex, Protein Tyrosine Phosphatase 1β, Diabetes, Metabolic Syndrome ¾ e w ƒ w wš ã ƒw m tw 2007 m w ( ), x y, y, š w ( ) 5 w w ( ) w w w &NBJM MJNTT!IBMMZNBDLS 5FM ƒw. 1) y 90% wš 2x ƒ ù y w e w x w š. 2-4) z e w wƒ» 2-3ƒ» š. w w š l w e w ƒ. 196

2 Vol. 40, No. 3, (Dioscoreae Rhizoma),,, w e, 5) w mw z, 6) w z, 7) w z, 8) w y z, 9) šx, 10), 11) 12) y. w š (Bombycis corpus) (Bombix mori) ³ (Beauveria bassiana) w t ( ª ), t m (ª ), zm (ž ) e š. 13) y p y p w š, 14) p ù w g (Rhynchosia nulubilis) w y z ƒ p ù šƒ ñš. 15) w w, 16) w, 17) x w 18). p Im w g x w w z y w. 19),, w, w y w z ƒ t (, g,, ƒ ) yww w w š w z streptozotocin šx k y w x» y w. x n-hexane, methylene chloride, n-butanol, ethyl acetate SKf e, streptozotocin, acarbose, α-glucosidase, p-nitrophenyl -α-d-glucopyranoside, sodium carbonate sigma-aldrich ƒƒ w w. PTP1β drug discovery kit (AK822, BIOMOL International LP, USA) BIOMOL w w. Rosiglitazone w w w w Kazuo Ohuchi l œ w. š, w w (Dioscoreae Rhizoma), g (Rhynchosia nulubilis), (Bombycis corpus), ƒ ƒ 100 g w z t w y w w (, w ) l œ w. w α-glucosidase PTP1β y sƒ w œ w w ethanol w. w w 100 g 2L š» (MS-CM709, Korea) w 100 o C wš (Whatman No. 2) w vl wš 3z w H 2 O -70 o C w z» (PVTFD10R, ilshin lab) w q xk H 2 O g (31.67%). w, w w 300 g 95% ethanol 3L š» w o C y w ethanol š, (Whatman No. 2) w vlw. 3z w ethanol w, ey w z w q xk ethanol g (13.97%).» ethanol zw» w z w., ethanol z w -x : (1:1 v/v) ƒ 1 L z, w. 3z w n-hexane y wš w n-hexane z g (4.19%). w û d ƒw z y w methylene chloride z (4.68 g, 1.56%), ethyl acetate z (6.66 g, 2.22%), n-butanol z (5.10 g, 1.7%) water z (12.46 g, 4.15%) y w w» ¾ -70 o C w. α-glucosidase wy d α-glucosidase wy d ½ xw w. 20) z 2.1 unit phosphate buffer (PBS) 2 ml 400 µl yww z 37 o C 10 k 0.55 mm p-nitrophenyl-α-d-glucopyranoside 1 ml ƒw 37 o C 10 g. 0.1 M sodium carbonate 1.6 ml ƒw jš 405 nm Ÿ d w w w. w (%) = {1-(Sample O.D/Control O.D)} 100 Control O.D: PBS ƒw x Ÿ Sample O.D: ƒw x Ÿ Protein tyrosine phosphatase 1β (PTP1β) y d PTP1β z y PTP1β drug discovery kit (AK822, BIOMOL International LP, USA) w protocol w., 100 mm methyl ethyl sulfide (MES) (ph 6.0) 0.3 M NaCl, 2 mm EDTA, 2 mm dithiothreitol (DTT) 0.1% NP-40 sw w k y rk» insulin receptor 5 (IR5) 75 µm PTP1β (2.5 ng/well) ƒ well x ƒw. 37 o C 30 k z BIOMOL RED TM ƒw k 620 nm Ÿ d w. w (%) = {1-(Sample O.D/Control O.D)} 100 Control O.D: PBS ƒw x Ÿ Sample O.D: ƒw x Ÿ PTP1β z y w GC-MS

198 Kor. J. Pharmacogn. w ethanol l n-hexaned y w» w 1 gas chromatography-mass spectrometer (GC/MS) w w.»» 6890N (Agilent, USA) w š, e DB-5MS (60 m 0.320 mm, 0.

3 198 Kor. J. Pharmacogn. w ethanol l n-hexaned y w» w 1 gas chromatography-mass spectrometer (GC/MS) w w.»» 6890N (Agilent, USA) w š, e DB-5MS (60 m mm, 0.25 mm) w, 50 o C 3 š, 200 C¾ o 10 C o z, 220 o C ¾ 5 o C š 15 w. Injector 250 o C, 1µL w. Carrier gas He w 0.5 ml/min w.» electron impact (EI) w š, ionization energy 70 ev, source temp. 250 o C, trap current 300 µa w, ƒƒ total ion chromatogram z NBS library w (tentatively) yw w. Streptozotocin x 180~200 g 4 f rat (Sprague Dawley) x l w, 23±1 o C, 60±5%, 60 phone w,» 20 ppm w, lux, 12» y œ w 1 y g. x w š w. 1 Fig. 1 (A) x wš, x 25 streptozotocin (STZ, 35 mg/kg) n w w. š 24 z Õ l œ x d w 250 mg/dl w w 8 w. w H 2 O n w. n n» y w w., n 60 kg 1z 3 g ( 40y) w 3z (9 g/60 kg)» w n ƒ w, kg 150 mg n w v wù, H 2 O 33% 1 50 mg/kg n w. w rosiglitazone n šw 10 mg/kg n w. x 2z d w. z x 20~25 g 4 f ICR mouse x l w, STZ y œ w 1 g. x w š w. z 5 š g z w. x w 8 w, Fig. 1(B). šx y wš, yww m w. kg (low dosage, LD) x 9 g, š Fig. 1. Protocols of animal experiment. (high dosage, HD) x 36 g yww 6 g. ƒ n 1z d w, 10 œ x 1z w. n 60 kg 1z 3 g ( 40y) w 3z w š w kg 150 mg w, x s³ (30 g) (5 g) w, 5g w 30mg y w., LD kg 9 g sw g, HD 4 36 g sw g w g. ü (Oral glucose tolerance test, OGTT) z OGTT xw, x 16 z w. Glucose 2 g/kg n wš 0min, 30 min, 60 min, 120 min, 180 min Õ l x w x d» (Accu check, Germany) w x d w. w STZ w, w w x diethylether

4 Vol. 40, No. 3, z w w wš 4 o C 10% paraformaldehyde 24 š w. š 5 w z» (Leica, Germany) w k w š, q v en k q v s» (EG 1150, Germany) q v w. j m (Leica, Germany) w 5µm Ì r w z xylene alcohol w kq v k Hematoxylin & Eosin (H&E) w z w jš, Ÿwx w. m w x s³±t r ùk ü x w m student s t-test w p<0.05 w ƒ q w. š α-glucosidase y α- w wš k y α-glucosidase w w z glucose k z x e ƒ j α-glucosidase z zx z š. 21) w H 2 O ethanol α-glucosidase wy Table 1 ùkü. w H 2 O 2.5, 1.25, 0.63 mg/ml α-glucosidase y ƒƒ 73.5%, 50.5%, 21.7% ww IC mg/ml, ethanol 60.6%, 42.3%, 16.3% ww IC mg/ml y. 0.8, 0.4, 0.08 mg/ml ƒƒ 69.3%, 46.7%, 38.2% wy (IC 50 =0.39 mg/ml) acarbose (x t t ) H 2 O 1/3 ƒ y ùkü. w Table I. Inhibitory effect of α-glucosidase activity Concentration (mg/ml) Inhibition (%) IC 50 (mg/ml) HC H 2 O ext HC EtOH ext Acarbose acarbose z 1/3 z ƒ w α-glucosidase z w yw q., w in vivo z x w ƒ w». x q š acarbose α-glucosidase w» w y q, m, ùküš w. l x w ƒ y w š, w l α- glucosidase w ƒ š š. 22) w l α-glucosidase wy y w w x w ƒ y w. PTP1β y GC-MS w y y w ƒ z PTP1β y Table II. Inhibitory effect of PTP1β activity Concentration (µg/ml) Inhibition (%) IC 50 (µg/ml) HC H 2 O ext NA 80 NA HC EtOH ext HC n-hex fr EtOH ext MC fr EtOAc fr n-buoh fr H 2 O fr Suramin 1.0 (0.8 µm) (0.4 µm) (0.57 µm) 0.1 (0.08 µm) NA: Non-active

5 200 Kor. J. Pharmacogn. Fig. 2. GC-MS chromatogram of the n-hexane fraction of ethanol extract from herbal complex (HC). Table III. Composition of n-hexane fraction of the ethanol extract from HC by GC-MS No. Retention time (min) Compounds Relative area (%) Palmitic acid Octadecanoic acid Methyl ester 8, Octadecanoic acid Methyl oleate Methyl ester 4- hydroxy Octadecanoic acid Ethyl linoleate Ethyl oleate Eicosanoic acid 2.42 Table 2 ùkü. w H 2 O y û (800 µg/ml 10.2% y ) ù, ethanol IC µg/ml suramin 0.57 µm (0.72 µg/ml) w w ù, w y. H 2 O ethanol y ethanol w y w q y wš ethanol z w. Table 2 ùkù z w wš, methylene chloride z wš, z w PTP1β y ù kü. z ƒ w y w n-hexane z (IC µg/ml) y w» w GC-MS w (Fig. 2, Table 3). n-hexane z GC-MS k y methyl, ethyl ester xk. š STZ ƒ z (food efficiency ratio, FER) š w STZ k y Fig. 3 ùkü. x 3 ¾ ƒ ƒ w. x ¾ ã ƒw, x STZ n z l w w. ù, ƒ x. z 0.26 ƒ z. w k z w ùkü (Table 4). 1x y ù w š, STZ w k s q w Fig. 3. Changes of body weight in STZ-induced diabetic rat. HC: Herbal complex, H-cont: High-fat diet control, H-HC: High-fat diet + herbal complex, H-STZ-cont: High-fat diet + streptozotocin control, H-STZ-HC: High-fat diet + streptozotocin + herbal complex, H-STZ-Rosi: High-fat diet + streptozotocin + rosiglitazone.

6 Vol. 40, No. 3, Table IV. Body weight, food intakes and food efficiency ratio (FER) in STZ-induced diabetic rats. Group Initial weight (g) Final weight (g) Change of body weight (g) Food intake (g) FER H-cont 209.7± ± ± H-HC 198.3± ± ± H-STZ-cont 202.9± ± ± H-STZ-Rosi 195.3± ±3.3** 145.1±2.9** H-STZ-HC 209.0± ±2.5** 149.2±1.3** Values are represent the mean±sd (n=8). **p<0.01 compared to diabetic (STZ) control. H-cont: High-fat diet control, H-HC: High-fat diet + herbal complex, H-STZ-cont: High-fat diet + streptozotocin control, H-STZ-HC: High-fat diet + streptozotocin + herbal complex, H-STZ-Rosi: High-fat diet + streptozotocin + rosiglitazone, HC: Herbal complex g s ü s,, ü w w z» Fig. 4. Changes in blood glucose levels during OGTT in STZinduced diabetic rat. HC: Herbal complex, H-cont: High-fat diet control, H-HC: High-fat diet + herbal complex, H-STZ-cont: High-fat diet + streptozotocin control, H-STZ-HC: High-fat diet + streptozotocin + herbal complex, H-STZ-Rosi: High-fat diet + streptozotocin + rosiglitazone.. 23) STZ w ³x» w. š STZ w (OGTT) w k ü y w» w oral glucose tolerance test (OGTT) w (Fig. 4, Table 5). Glucosen z x še x e. x w w w glucose n 30 û x ù. w, STZ glucose n z ƒƒ 495.0±10.6 mg/dl 494.3±1.2 mg/dl w ƒ ±12.3 mg/dl ü y w. x w 2x e rosiglitazone n w glucose n z ±28.9 mg/ dl 442.8±10.84 mg/dl s³ 60 mg/dl x ƒ z ƒ y, rosiglitazone mw w» ew. 24) w, w n w ±5.5 mg/dl, 456.1±21.1 mg/dl w s³ mg/dl x Table V. Changes in blood glucose levels during OGTT in STZ-induced diabetic rat (mg/dl) Group Time (min.) H-cont 084.3± ± ± ± ±7.0 H-HC 094.2± ± ± ± ±2.9 H-STZ-cont 328.7± ± ± ± ±1.8 H-STZ-Rosi 331.4± ±28.9* 442.8±10.8* 353.3± ±12.1 H-STZ-HC 322.0± ±5.5* 456.1±21.1* 357.9± ±5.5 Values are represent the mean±sd (n=8). **p<0.01 compared to diabetic (STZ) control. H-cont: High-fat diet control, H-HC: High-fat diet + herbal complex, H-STZ-cont: High-fat diet + streptozotocin control, H-STZ-HC: High-fat diet + streptozotocin + herbal complex, H-STZ-Rosi: High-fat diet + streptozotocin + rosiglitazone, HC: Herbal complex

7 202 Kor. J. Pharmacogn. Morphology of pancreas. Hematoxylin and eosin-stained paraffin sections of pancreas from high-fat diet control (A), high-fat diet + streptozotocin control (B), high-fat diet + streptozotocin + herbal complex (C) and high-fat diet + streptozotocin + rosiglitazone (D) treated rat. Magnification of histological section 200 Fig. 5. 당증가 억제 효능을 가지는 것으로 확인되었다. 이는 생약 복합제의 PTP1β 효소를 효과적으로 억제하는 등의 기능에 의하여 인슐린 작용 기능의 개선에 의한 당부하능에 대한 기능개선 효능이라고 판단된다. 고지방식이 및 저용량 유도 당뇨쥐의 조직학적 검 사 췌장에 대한 조직병리학적 검사 결과, 시료나 약물을 투여하지 않은 동물군은 랑겔한스 섬의 상태가 심각하게 파 괴되어 있었고, rosiglitazone을 투여한 동물은 비교적 원형 모습을 유지하고 있었다. 그러나, 생약복합제를 투여한 동 물군에서는 췌장의 랑겔한스 섬의 형태가 당뇨대조군과 큰 차이를 보이지 않아, 병변이 호전되었다고 판단하기에는 미 흡하였다 (Fig. 5). 대사성증후군 모델의 체중 및 혈당 변화량 식이효율 고지방식이로 대사성증후군을 유발시킨 mice의 실험기간동 안 체중 및 혈당의 변화량은 Fig. 6에, 식이효율은 Table 6 에 나타내었다. 체중변화에 대해서는 개체간 편차는 있었으 나 모든 실험군에서 꾸준한 체중 증가가 관찰되었다. 시료 섭취군의 체중증가량은 대조군에 비해 낮게 나타났으나 HD 와 LD군 간 섭취량에 따른 유의적 차이는 없었다. STZ, Changes of body weight and fasting blood glucose level in high-fat diet induced metabolic syndrome mice. Values are represent the mean±sd (n=8). *p<0.05 and ***p<0.001 compared to high-fat diet control. Fig. 6. 혈당 변화에서는 대조군의 경우 고지방식이 섭취 8주 경 과 후 현저한 공복 혈당 상승을 관찰 할 수 있었으나, HD 군과 LD군은 공복혈당 상승 폭을 줄이는 효과를 보였다. 그 러나 두 시료투여군 사이에 유의적인 차이는 없었다. 이는 실험 종료 12주차까지 지속되는 것으로 확인되었다. 대사성증후군 모델의 경구당부하능 검사 대사 성증후군 모델에서 생약복합제를 투여한 동물에서 내당능 정도를 확인하기 위해서 OGTT를 실시하였다 (Fig. 7, Table 7). 실험동물에 2 g/kg 용량으로 glucose을 투여한 후 시간 (OGTT) Body weight, food intakes and food efficiency ratio (FER) in mice of metabolic syndrome Group Initial weight (g) Final weight (g) Change of body weight (g) Food intake (g) 46.3± ± High-fat diet control 36.3± ± ±0.3** 235 High dosage 36.2± ± ±0.5** 243 Low dosage 36.5±0.4 Table VI. Values are represent the mean±sd (n=8). **p<0.01 compared to diabetic control. FER

8 Vol. 40, No. 3, Table VII. Changes in blood glucose levels during OGTT in mice of metabolic syndrome (mg/dl) Group Time (min.) High-fat diet control 150.2± ± ± ±10.3 High dosage 098.2±7.7** 228.3± ± ±15.7*** Low dosage 099.9±12.3** 231.0± ±8.5** 145.3±10.3*** Values are represent the mean±sd (n=8). **p<0.01, ***p<0.001 compared to high-fat diet control. Fig. 7. Changes in blood glucose levels during OGTT in metabolic syndrome mice. Values are represent the mean±sd (n=8). **p<0.01 and ***p<0.001 compared to high-fat diet control. x y r. x»x eƒ ƒ ùkù glucose n z 30 ƒ š, 60 p z 120 w n n x w w ù w HD LD ùkù. w w w x z q. xw š STZ OGTT glucose n z 30 x 495 mg/dl n» w ùkû ù, z z z ùkù z kƒ» xk šx ( glucose n z30 x 250 mg/dl )» z ùkù q. z šx, œ šx ùkù w. 25) z šx jš» w g j k y jš, x w x w k š š. 26) e z x e ƒà w w, x w w zšx w w ƒ». w α-glucosidase PTP1β w z ùkü, ƒ l yw ƒ x w f α-glucosidase PTP1β z ƒ wù w z y y w. w ƒ» w ƒ w q. e m t w,, g, ƒ w x x m w x w z y w. w H 2 O w α-glucosidasez acarbose (IC 50 =0.39 mg/ml) w 1/3 y (IC 50 =1.24 mg/ml), ethanol ü w PTP1β z (IC 50 = µg/ml) z w. PTP1β z w n-hexane z w GC-MS w ùkû. š STZ (35 mg/ kg) k OGTT x rosiglitazone( w 30 z s³ 60 mg/dl ) w n w z ( w 30 z s³ 30 mg/dl ) y w. w, z ƒ z œ x ƒ x w y w, OGTT z x w w z w. k,, g, w w z x w q.

9 204 Kor. J. Pharmacogn. w» w» (MOEHRD, KRF J00503) w,. x 1. m (2008) 2007 m American Diabetes Association. (2001) Report of the expert committee on the diagnosis and classification of diabetes mellitus. Diabetes Care. 26: s5-s Cavaghan, M. K., Ehrmann, D. A. and Polonsky, K. S. (2000) Interactions between insulin resistance and insulin secretion in the development of glucose intolerance. J. Clin. Invest. 106: Inzucchi, S. E. (2002) Oral hypoglycemic therapy for type 2 diabetes. J. Am. Med. Assoc. 287: , ³. (2000),, Choi, E. M., Koo, S. J. and Hwang, J. K. (2004) Immune cell stimulating activity of mucopolysaccharide isolated from yam (Discorea batatas). J. Ethnopharmacol. 91: Kim, M. J., Kim, H. N., Kang, K. S., Baek, N. I., Kim, D. K., Kim, Y, S., Kim, S. H. and Jean, B. J. (2004) Methanol extract of Dioscorea Rhizoma inhibits pro-inflammatory cytokines and mediators in the synoviocytes of rheumatoid arthritis. Intern. Immunopharmacol. 4: Hu, K. and Yao, X. (2003) The cytotoxicity of methyl protoneogracillin (NSC ) and gracillin (NSC ), two steroidal saponins from the rhizomes of Dioscorea collettii var. hypoglauca, against human cancer cells in vitro. Phytother. Res. 17: Hou, W. C., Lee, M. H., Chen, H. J., Liang, W. L., Han, C. H., Liu, Y. W. and Lin, Y. H. (2001) Antioxidant activities of dioscorins, the storage protein of yam (Dioscorea batatas Decne). J. Agric. Food. Chem. 49: McAnuff, M. A., Harding, W. W., Omoruyi, F. O., Jacobs, H., Morrison, E. Y. and Asemota, H. N. (2005) Hypoglycemic effects of steroidal sapogenins isolated from Jamaican bitter yam, Dioscorea polygonoides. Food Chem. Toxicol. 43: Kwon, C. S., Sohn, H. Y., Kim, S. H., Kim, J. H., Son, K. H., Lee, J. S., Lim, J. K. and Kim, J. S. (2003) Anti-obesity effect of Dioscorea nipponica Makino with lipase-inhibitory activity in rodents. Biosci. Biotechnol. Biochem. 67: Chen, H. L., Wang, C. H., Chang, C. T. and Wang, T. C. (2003) Effects of Taiwanese yam (Dioscorea japonica Thunb va. Pseudojaponica Yamamoto) on upper gut function and lipid metabolism in Balb/c mice. Nutrition. 19: Pharmacopoeia Commission of the Ministry of Public Health, P.R. China. (1995) A coloured atlas of the Chinese material medica specified in pharmacopoeia of the people s republic of China. Guangdong science & technology press Abrams, J. J., Ginberg, H. and Grundy, S. M. (1982) Metabolism of cholesterol and plasma triglycerides in non-ketotic diabetes mellitus. Diabetes. 31: Sa, J. H., Shin, I. C., Jeong, K. J. and Shin T. H. (2003) Antioxidative activity and chemical characteristics from different organs of small black soybean (Yak-Kong) grown in the area of Jungsun. Korean J. food Sci. Technol. 35: Yoon, K. D., Kwon, D. J., Hong, S. S., Kim, S. I. and Chung, K. S. (1996) Inhibitory effect of soybean and fermented soybean products on the chemically induced mutagenesis. J. Microbiol. Biotechnol. 24: Chung, K. S., Yoon, K. D., Dwon, D. J., Hong S. S. and Choi, S. Y. (1997) Cytotoxicity testing of fermented soybean products with various tumour cells using MTT Assay. J. Microbiol. Biotechnol. 25: Kil, J. O., Kim, G. N. and Park, I. S. (1998) Production and characterization of fibrinolytic enzyme: Optimal condition for production of the enzyme from Bacillus sp. KP isolated from Chungkook - jang. J. Korean Soc. Food Sci. Nutr. 27: Im, C. M., Kwon, S. H., Bae, M. S., Jung, K. O., Moon, S. H. and Park, K. Y. (2006) Characteristics and increased antimutagenic effect of black soybean (Var. Seoritae) chungkukjang. Cancer Prev. Res. 11: Kim, Y. M., Jeong, Y. K., Wang,, M. H., Lee, W. Y. and Rhee, H. I. (2005) Inhibitory effect of pine extract on α-glucosidase activity and postprandial hyperglycemia. Nutrition. 21: Godbout, A. and Chiasson, J. L. (2007) Who should benefit from the use of alpha-glucosidase inhibitors? Curr. Diab. Rep. 7: Matsui, T., Ogunwande, I. A., Abesundara, K. J. and Matsumoto, K. (2006) Anti-hyperglycemic Potential of natural products. Mini. Rev. Med. Chem. 6: Pain, V. M. and Garlick, P. J. (1974) Effect of streptozotocin diabetes and insulin treatment on the rate of protein synthesis in issues of the rat in vivo. J. Biol. Chem. 249: Miyazaki, Y. l., Glass L., Triplitt, C., Matsuda, M., Cusi, K., Mahankali, A., Mahankali, S., Mandarino, L. J. and DeFronzo, R. A. (2001) Effect of rosiglitazone on glucose and non-esterified fatty acid metabolism in Type II diabetic patients. Diabetologia. 44: Defronzo, R. A. (1981) The effect of insulin on renal sodium metabolism. Diabetologia. 21: Young, I. R. and Stout, R. W. (1987) Effects of insulin and glucose on the cells of the arterial wall: Interaction of insulin with dibutyryl cyclic AMP and low density lipoprotein in arterial cells. Diabetes Metab. 13: ( )

Pharmacotherapeutics Application of New Pathogenesis on the Drug Treatment of Diabetes Young Seol Kim, M.D. Department of Endocrinology Kyung Hee Univ

Pharmacotherapeutics Application of New Pathogenesis on the Drug Treatment of Diabetes Young Seol Kim, M.D. Department of Endocrinology Kyung Hee Univ Application of New Pathogenesis on the Drug Treatment of Diabetes Young Seol Kim, M.D. Department of Endocrinology Kyung Hee University College of Medicine & Hospital E mail : ycell2@yahoo.co.kr Abstract