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1 J Korean Soc Food Sci Nutr 한국식품영양과학회지 43(11), 1658~1664(2014) 고지방식이와 STZ 유도제 2 형당뇨마우스에서새싹의항당뇨효과 이현서 1 강현주 2 전인화 2 염정호 3 장선일 1,2 1 전주대학교보건관리학과 2 ( 주 ) 아토큐앤에이 3 전북대학교예방의학과 Anti-Diaetic Effects of Sprouts in High-Fat Diet and Streptozotocin- Induced Type Ⅱ Diaetes Mellitus Mice Hyun-Seo Lee 1, Hyun Ju Kang 2, In Hwa Jeon 2, Jung Ho Youm 3, and Seon Il Jang 1,2 1 Department of Health & Science, Jeonju University 2 Ato Q&A Incoperation 3 Department of Preventive Health Medicine, Chonuk National University Medical School ABSTRACT Sprout vegetales containing various types of polyphenols and flavonoids, are known to have anti-inflammatory, antioxidant, cholesterol-lowering, and anti-oesity activities. However, there have een few reports on the anti-diaetic efficacy of sprout vegetales. Here, we investigated the anti-diaetic effects of sprout extract otained from uckwheat, eet, rape, roccoli, kohlrai, red young radish, and dachai, in high fat diet (HFD) and streptozotocin (STZ)-induced type Ⅱ diaetes mellitus mice. The mice were fed a HFD (60% calories as fat) for 8 weeks prior to intraperitoneal injection with STZ (75 mg/kg). The diaetic mice were divided into four groups: standard diet (STD, % calories fat), HFD, HFD with sprout extract (SPE) and HFD with metformin (MET). After 4 weeks, ody weight gain was much lower in oth SPE and MET groups than in HFD group. In contrast, there was no difference experiment groups regarding food intake ratio. The level of fasting lood glucose was significantly lower in the SPE and MET groups compared to the HFD group. Oral glucose tolerance and insulin tolerance in the SPE and MET groups were significantly ameliorated in comparison to the HFD group. The concentrations of serum total cholesterol, triglycerides, and LDL cholesterol in the SPE and MET groups were remarkaly reduced in comparison to the HFD group, and HDL cholesterol concentration was higher in the SPE and MET groups than in the HFD group. Glutamate oxaloacetate transaminase and glutamate pyruvate transaminase levels were etween SPE and HFD groups. The serum insulin and leptin concentrations were significantly reduced in oth the SPE and MET groups compared to the HFD group. Therefore, these results indicate that sprout extract could improve insulin resistance and attenuate lood glucose level in HFD/STZ-induced type Ⅱ diaetes mellitus mice. We conclude that this study may provide positive insights into sprout extract as a functional food ingredient for treatment of type Ⅱ diaetes mellitus. Key words: sprout vegetales, type Ⅱ diaetes mellitus, glucose tolerance, insulin, leptin 서 대사성질환의대표적인당뇨병은비만과함께단일질환으로는가장많은의료비를사용하고있으며그수는기하급수적으로증가하고있는실정이다. 당뇨병은췌장 β세포에서인슐린의절대량부족으로야기되는제1형과말초조직에서발생하는인슐린저항성에의해정상적인생리기능을수행하지못하는제2형으로나눌수있다. 과다한단백질과지방섭취등잘못된생활습관으로야기되는당뇨가주로 Received 24 June 2014; Accepted 26 Septemer 2014 Corresponding author: Seon Il Jang, Department of Health & Science, Jeonju University, Jeonuk , Korea sonjjang@jj.ac.kr, Phone: 론 제2형당뇨병에해당되며, 성인뿐만아니라청소년들에서도발병하고있는추세여서치료제개발을위한다양한노력들이심화되고있다 (1-3). 제2형당뇨병의주요병인인비만, 특히복부비만이인슐린저항성을일으키는원인으로관심을받고있으며복부비만과인슐린저항성그리고만성염증상태가서로연관되어있다는것이알려졌다. 따라서비만으로인한만성염증상태를경감시키고인슐린저항성개선을통한혈당조절을타깃으로제2형당뇨를치료하는데주목하고있다 (4,5). 새싹은완전히성장한채소와비교했을때폴리페놀과플라보노이드성분이풍부해항산화, 항염및콜레스테롤억제효과가있으며인체내에서발생하는활성산소종에의한장기와조직손상및면역력저하에탁월한예방과치료효능

2 제 2 형당뇨마우스에서새싹의항당뇨효과 1659 이있다 (6-8). 습관적으로고칼로리식품을섭취하는당뇨환자의경우효과적인체중관리를위해새싹과같이독성이없는천연항산화물질과항염효과가우수한식이섬유섭취가필수적이며, 산화적스트레스로인한췌장 β세포의기능장애개선에도도움이될수있을것으로생각한다. 일반적으로당뇨치료는약물치료와운동그리고계획된식이요법을병행함으로써혈당이조절되게한다. 현재제2형당뇨치료제로써널리사용되고있는메트포민은 glycogen의분해율을감소시켜혈당치를낮추고췌장으로부터인슐린분비도촉진하지않으며, 체중감소효과도나타낸다. 또한인슐린유무와상관없이지방산산화에영향을미쳐혈장지질감소에도좋은효과를나타낸다 (9). 하지만메트포민치료요법의주요부작용은구토, 복부불쾌감이나복부팽만감등소화기계통에서주로많이나타나며이러한부작용으로인해당뇨치료를중단하는경우가상당히많다고보고되고있다. 당뇨환자가메트포민을장기복용한경우체내칼슘대사에영향을미쳐비타민 B 12 의흡수를저해함으로써피로감을동반한혀의통증이나신경증을유발할수있다. 메트포민은소장점막에서당을젖산으로전환시키는데, 일부신장기능이저하된당뇨환자에게지속적으로메트포민을투여한경우혈액내축적된메트포민이간에서젖산이당으로전환되는것을저해하여혈액내젖산농도가올라가게되고호흡곤란이나복부통증등을일으키는젖산산증을유발한다. 이와같이신장기능이약하거나심장질환자그리고간기능이약한환자에게사용시심각한부작용을초래할수도있다 (-12). 따라서이와같은부작용을최소화하고장기적으로복용시안전하며인슐린저항성을감소시켜정상적으로인슐린분비를촉진함으로써비정상적인혈당상승조절을가능하게하는천연자원식품소재개발이절실하게요구되고있다. 그러므로본연구에서는고지방식이와 streptozotocin(stz) 으로유도한제2형당뇨마우스에서새싹추출물의항비만, 지질대사정상화, 혈당조절및인슐린저항성개선의효과가있는지조사해봄으로써제2형당뇨질환치료에있어서우수한식품소재로서의가능성을확인하였다. 재료및방법고지방식이및 STZ에의한제2형당뇨마우스모델제작 4주령 C57BL/6 수컷마우스를 중앙실험동물 ( 서울, 한국 ) 로부터구매하여적절한온도 (22±2 C) 와습도 (50±5 C) 를유지하며 12시간주기로명암을조절하면서 1주간적응시켰다. 고지방식이 (HFD) 와표준식이 (STD) 군의사료 (Tale 1) 는 Research Diet Inc.(New Brunswick, NJ, USA) 에서구입하여사용하였으며, 표준식이 (STD) 군을제외한실험군들은인슐린저항성을유도하기위해고지방식이를 8주간급여하였다. 고지방식이 (HFD) 급여 8주후췌장세포의부분적손상에의한당뇨유발을위해 STZ를 0.1 Tale 1. Ingredient and chemical composition of diets Experimental groups 1) Ingredient STD (g) HFD (g) Casein L-Cystine Corn starch Maltodextrin Sucrose Cellulose Soyean oil Lard Mineral mix S026 Dicalcium phosphate Calcium caronate Potassium citrate Vitamin mix V001 Choline itartrate Protein Carohydrate Fat kcal/gram Gm% Gm% ) STD: standard diet with % fat calories, HFD: high fat diet with 60% fat calories. M citrate 용액 (ph 4.5) 에녹여체중 kg당 75 mg(75 mg/kg ody weight) 을일회복강주사하였다. STZ 주사 1주일째 12시간이상마우스를금식시킨후혈당측정결과혈당이 mg/dl인마우스만을비만형제2형당뇨병유발마우스로간주하여추후실험에사용하였다. 모든동물실험과정은전주대학교동물실험윤리위원회의승인을받았다 (No ). 열수추출물제조실험에사용한새싹들 (sprouts) 은전라북도진안군진안읍애농영농조합으로부터공급받았다. 새싹열수추출에사용된새싹들 ( 메밀 : uckwheat, 비트 : eet, 유채 : rape, 브로컬리 : roccoli, 콜라비 : kohlrai, 적양무 : red young radish, 비타민 : dachai) 의기본조성비율은 Tale 2와같다. 건조된새싹들은 0 g으로정량하여증류수 1,000 ml 를주입하고 5분간끓인후얻어진추출물을 0.45 μm 필터 Tale 2. Composition ratio of experimental extract Experimental extract 1) Ingredient SPE (g) Buckwheat Beet Rape Broccoli Kohlrai Red young radish Dachai Total 0 1) SPE: sprout extract.

3 1660 이현서 강현주 전인화 염정호 장선일 Fig. 1. Schedule for treatment of mice in experiment for 13 weeks. Type Ⅱ diaetic mice were divided to 4 groups such as STD, HFD, HFD+SPE, and HFD+MET. The serum collection was performed for various analyses every 2 weeks and at the last week efore sacrificing mice. STD, standard diet (% fat calories); HFD, high fat diet (60% fat calories); SPE, sprout extract; MET, metformin; OGTT, oral glucose tolerance test; FBG, fasting lood glucose; SI & SL, serum insulin & serum leptin; GOT, glutamate oxaloacetate transaminase; GPT, glutamate pyruvate transaminase; ITT, insulin tolerance test. 를사용하여여과한다음동결건조기 (EYELA FDU-20, Tokyo, Japan) 에서건조하여분말형태로회수하였다. 회수한새싹추출물 (SPE) 9.8 g을 -20 o C에서보관하면서실험에사용하였다. 실험군선정및추출물투여계획식이급여와투여에따른실험분석스케줄은 Fig. 1과같다. 표준식이군 (STD, % fat calories) 을제외하고비만형제2형당뇨병이유발된 C57BL/6 마우스를각실험군당 마리씩나누고고지방식이군 (HFD, 60% fat calories), 고지방식이와새싹추출물투여군 (SPE) 그리고고지방식이군과메트포민 (MET) 투여군으로나누어 4주간사육하였다. 새싹추출물과메트포민은 300 mg/kg ody weight로 0 μl 씩매일오전 9 시사이에경구투여용존데를사용하여 4주동안투여하였으며, 표준식이군과고지방식이군은동일한양의증류수를경구투여하였다. 체중과식이섭취량측정체중은실험시작일에최초측정한다음매주 1회실험종료일까지 4주에걸쳐측정하였고식이섭취량은투여기간동안주당 2회측정하였다. 식이섭취량은이전사료공급량에서잔량을감하여계산하였다. 혈청채취실험동물은 2주마다 12시간금식시킨후에테르마취를하지않고마우스고정틀안에마우스를삽입한다음꼬리로부터공복혈액을채취하였다. 채취한혈액은 3,000 rpm (4 C) 에서 15분간원심분리하여혈청을분리하였으며혈청의생화학적분석전까지 -70 C에보관하였다. 공복혈당, 경구내당능및인슐린내성측정공복혈당 (fasting lood glucose, FBG) 측정은 2주마다한번씩꼬리정맥에서채혈하였으며, 채혈전 12시간동안금식시킨후혈당측정기 (Acuu-Check, Roche Diagnostics Korea Co., Ltd., Seoul, Korea) 를이용하여각그룹에 대한혈당변화를관찰하였다. 경구내당능 (oral glucose tolerance test, OGTT) 검사는실험종료 3주째에 12시간금식시킨후포도당용액을체중 kg당 1 g씩경구투여한다음 0, 30, 60, 90, 120분후마우스꼬리정맥에서혈액을채취하여혈당을측정하였다. 인슐린내성검사 (insulin tolerance test, ITT) 는실험종료마지막주에 12시간금식시킨후인슐린용액을체중 kg당 1 unit씩복강주사한다음 0, 30, 60, 90, 120분후마우스꼬리정맥에서혈액을채취하여혈당을측정하였다. 혈중지질농도분석혈청지질농도 (lipid profile) 분석을위해측정용 kit(am 202-K, AM 203-KTC, AM 157S-K, Asan Pharm. Co., Seoul, Korea) 로 TC(total cholesterol), HDL(high density cholesterol), LDL(low density cholesterol) 및 TG (triglyceride) 를측정하였다. LDL 함량은 Friedewald 등 (13) 의공식에의해 [ 총콜레스테롤-HDL 콜레스테롤-( 중성지방 /5)] 로계산하였다. 혈중 GOT와 GPT 활성측정혈청 glutamate oxaloacetate transaminase(got) 와 glutamate pyruvate transaminase(gtp) 의활성은 Reitman과 Frankel(14) 의방법에따라측정용키트 (Asan Pharm. Co.) 를사용하여측정하였다. 혈청중 GOT, GTP의활성도는표준검량곡선에서산출하였으며혈청 1 ml당 IU/ L로나타내었다. 혈중인슐린과렙틴농도측정혈청인슐린농도와렙틴농도는 ultra sensitive mouse insulin ELISA kit(crysral Chem Inc., Downers Grove, IL, USA) 와 mouse leptin Quantikine ELISA kit(r&d systems, Inc., Minneapolis, MN, USA) 를사용하여 immunoassay로측정하였다.

4 제 2 형당뇨마우스에서새싹의항당뇨효과 1661 통계처리모든실험값은평균 ± 표준편차 (mean±sd) 로표시하였고, 통계학적비교분석은 SPSS Statistics 19(IBM, New York, NY, USA) 를이용하였고각실험군간의비교는 one-way analysis of variance(anova) 로처리하였으며, 실험군들과의유의차를알아보기위한다중비교방법으로 Duncan's multiple range test 검정을실시하였다. 검정유의도는 P 값이 0.05 미만수준일때를기준으로하였다. 결과및고찰 체중과식이섭취량에미치는영향고지방식이와저농도 STZ의투여는인슐린저항성과함께고인슐린증을일으키는췌장 β세포의선택적인파괴를유도해제2형당뇨병을유발한다. 본연구에서는이와같은방법으로제2형당뇨병을유발시킨후 4주동안새싹추출을투여하여체중및식이섭취량을관찰하였다 (Fig. 1). 제2형당뇨병을유발후실험개시전에실험군의평균체중을측정한결과 (Tale 3), 표준식이군을제외한나머지실험군의평균체중 (33.06±0.75) 에는유의적인차이가없었다. 실험종료일에고지방식이군 (36.31±2.72) 의체중은표준식이군 (24.97±1.15) 보다유의적으로증가하였으며, 새싹추출물군 (34.01±1.19) 과메트포민투여군 (32.13±2.11) 은고지방식이군보다유의성있는감소를보였다. 평균증체량은새싹추출물군 (1.38±1.75) 과메트포민군 (-1.17±2.31) 이고지방식이군 (3.04±3.22) 에비해각각 %, -138% 로유의적 (P<0.05) 으로감소하였다. 식이섭취량은모든실험군에서유의적인차이가없으므로식이섭취량은체중감소와관계가없음을알수있다. 비만은당뇨병발병에주요병인으로체중감량은당뇨병발생을현저하게감소시켜체중과당뇨병이밀접하게관련있음이입증되었고, d/d 마우스에서체중감소는인슐린저항성과혈당조절효과에영향을미치는것으로알려져있다 (15,16). 본연구결과를통해새싹추출물은제2형당뇨병에있어서항비만효과를보여주고이와관련된인슐린저항성과혈당조절에긍정적인영향을줄것으로생각된다. 혈당, 경구내당능및인슐린내성에미치는영향새싹추출물을 4주동안투여한제2형당뇨마우스의혈당 Fig. 2. Effect of sprout extract on fasting glucose level in HFD/ STZ-induced type Ⅱ diaetic mice. Groups are the same as in Tale 3. Values represent mean±sd for mice in each group. Means in the same time not sharing common letters (a-c) are significantly different y Duncan's multiple range test (P<0.05). 변화는 Fig. 2와같다. 실험개시전표준식이군 (127. ±5.87) 을제외한실험군간의혈당 (230±12.53) 은차이가없었으며표준식이군의혈당은실험기간동안거의일정하게유지되었으나고지방식이군의경우실험기간동안지속적인혈당상승이관찰되었다. 특히실험종료 4주째새싹추출물군 (235.53±36.35) 과메트포민군 (182.57±30.61) 은고지방식이군 (325.41±63.62) 에비해각각 %, % 로유의성있는혈당감소를나타냈다. 경구내당능결과는포도당섭취후 60분, 90분에서새싹추출물군과메트포민군이고지방식이군보다유의성있게혈당이감소하였음을알수있으며, 120분에서새싹추출물군 (216.28±11.22) 과메트포민군 (215.40±39.20) 은고지방식이군 (322.30±32.80) 에비해각각 %, % 유의적으로혈당이감소하였다. 또한 120분에서새싹추출물군과메트포민군의혈당은포도당투여전혈당수준으로떨어진반면고지방식이군은포도당투여전혈당보다높았다 (Fig. 3A). 인슐린내성결과는인슐린투여 120분에서새싹추출물군 (181.22±12.84) 과메트포민군 (168.00±11.01) 이고지방식이군 (241.67±18.98) 보다유의성있게혈당이감소하였음을알수있다 (Fig. 3B). 이와같은결과를통해새싹추출물은제2형당뇨마우스에서인슐린저항성을감소시키고혈당강하의효과가있는것으로생각된다. Tale 3. The ody weight and food consumption in high-fat/stz-induced diaetic mice Body weight (g) Experimental groups 1) STD HFD SPE MET Initial Final Food intake (g/week) 22.58±0.95 a2) 24.97±1.15 a 17.62±3.31 a 33.27± ±2.72 d 16.51±2.91 a 32.63± ±1.19 c 16.13±2.47 a 33.30± ± ±2.91 a 1) STD: fed standard diet with % fat calories, HFD: fed high fat diet with 60% fat calories, SPE: fed high fat diet with 60% fat calories and administered with sprout extract, MET: fed high fat diet with 60% fat calories and administered with metformin. 2) Means in the same row not sharing common letters are significantly different y Duncan's multiple range test (P<0.05).

5 1662 이현서 강현주 전인화 염정호 장선일 A B Fig. 3. Effect of sprout extract on oral glucose tolerance test (A) and insulin tolerance test (B) in HFD/STZ-induced type Ⅱ diaetic mice. Groups are the same as in Tale 3. Values represent mean±sd for mice in each group. Means in the same time not sharing common letters (a-c) are significantly different y Duncan's multiple range test (P<0.05). 혈중지질농도의변화와 GOT와 GPT 활성측정새싹추출물의혈중지질조성에대한효과를살펴본결과총콜레스테롤농도는고지방식이군 (287.53±15.13) 이새싹추출물군 (208.06±11.96) 과메트포민투여군 (233.93± 14.76) 에비하여유의적으로증가하였다. 중성지방농도는새싹추출물군 (83.95±13.33) 과메트포민투여군 (5.25± 21.44) 이고지방식이군 (154.29±20.70) 보다각각 -45%, -32% 유의성있게감소하였으며표준식이군 (6.67± 21.19) 의지질농도수준으로감소하였다 (Tale 4). 새싹추출물군 (91.67±6.86) 과메트포민투여군 (89.14±9.15) 의 HDL 콜레스테롤농도는고지방식이군 (82.63±5.70) 보다유의성있게높았으나 LDL 콜레스테롤농도는고지방식이군 (174.25±42.45) 보다새싹추출물군 (6.50±14.99) 과메트포민투여군 (139.83±38.37) 에서각각 -38%, -20% 유의적으로감소하였다. 새싹추출물이간독성에미치는영향을알아보기위해혈중 GOT와 GPT 효소활성도를검사한결과새싹추출물군 (21.50±9.22) 과고지방식이군 (25.90±.02) 간에 GOT 효소활성도는차이를보이지않았으며, GPT 활성도는모든실험군들간에유의한차이가없었다. 당뇨병으로인한인슐린저항성및고인슐린증상태에서는지방조직에있는유리지방산의분해가증가되어간에서지방합성및 VLDL (very low density lipoprotein) 의생성이증가되고지단백리파아제활성화가감소되어혈중중성지방이증가될수있다. 또한혈중중성지방의증가로인해 HDL 농도가감소하고 LDL 농도가증가한다고알려져있다 (17-19). 이와같이당뇨로인한혈중지질대사이상은당뇨병치료의주요바이오마커이며, 당뇨병치료에있어서이상지질혈증의정상화는매우중요한부분이라고할수있다. 본연구결과새싹추출물이혈중 HDL 콜레스테롤농도를증가시키고중성지방과 LDL 콜레스테롤농도를유의적으로감소시켰음을알수있었으며, 이러한효과는새싹추출물이당질흡수를느리게하고간과근육에지방축적을감소시킴으로써혈중지질대사이상을억제시켜인슐린민감성을개선하고혈당을정상화하는데관여할것으로생각된다. 혈중인슐린및렙틴농도에미치는영향인슐린저항성이비만형제2형당뇨와같은대사성증후군의가장핵심적인요인이므로혈중인슐린농도측정은인슐린감수성및저항성을측정할수있는중요한표식마커이다. 혈중인슐린농도는표준식이군 (0.1±0.08) 보다고지방식이군 (0.92±0.06) 에서유의적으로증가하였고, 새싹추출물투여군 (0.56±0.19) 과메트포민투여군 (0.36±0.11) 은고지방식이군 (0.92±0.06) 에비해각각 -40% 와 -61% Tale 4. Effect of sprout extract on serum lipid profile and transaminase in HFD/STZ-induced type Ⅱ diaetic mice Parameters Experimental groups STD HFD SPE MET TC TG HDL LDL 1) GOT GPT ±11.94 a2)3) 6.67±21.19 a 96.60± ±37.02 a 19.40±6.53 a 4.82±3.48 a ±15.13 c ± ±5.70 a ±42.45 c 25.90± ±6.03 a ±11.96 a 83.95±13.33 a 91.67± ±14.99 a 21.50±9.22 a 5.09±5.36 a ± ±21.44 a 89.14± ± ±3.09 a 4.49±3.11 a 1) LDL cholesterol=[total cholesterol-hdl cholesterol-(triglyceride/5)], GOT: glutamate oxaloacetate transaminase, GPT: glutamate pyruvate transaminase. 2) Values represent mean±sd for mice in each group. 3) Means in the same row not sharing common letters are significantly different y Duncan's multiple range test (P<0.05).

6 제 2 형당뇨마우스에서새싹의항당뇨효과 1663 A B c c a a Fig. 4. Effect of sprout extract on serum insulin (A) and leptin (B) in HFD/STZ-induced type Ⅱ diaetic mice. Groups are the same as in Tale 3. Values represent mean±sd for mice in each group. Means on the ars not sharing common letters (a-c) are significantly different y Duncan's multiple range test (P<0.05). 유의적으로감소하였다 (Fig. 4). 고지방식이군에서나타나는지속적인혈당증가 (Fig. 2) 와함께현저하게증가된혈중인슐린농도는인슐린저항성과인슐린매개포도당흡수의실패를입증해준다. 이와대조적으로새싹추출물군의경우새싹추출물투여종료일에관찰된유의적인혈당감소 (Fig. 2) 와함께인슐린민감성을개선할수있는소재로서긍정적인가능성을시사해준다. 혈중렙틴농도는정상군 (0.21±0.14) 에비해고지방식이군 (1.99±0.48) 에서유의하게증가하였으며, 새싹추출물투여군 (1.19±0.22) 과메트포민투여군 (0.95±0.39) 은고지방식이군 (1.99±0.48) 에비해각각 -40%, -52% 유의하게감소하였다. 렙틴은지방세포에서분비되며혈관뇌장벽 (loodrain arrier) 을통과하여시상하부에있는렙틴수용체에결합하여에너지균형과글루코스대사조절에관여하는호르몬으로식욕감소와에너지소비를증가시키는역할을한다 (20,21). 렙틴을 o/o 마우스에투여했을때체지방감소를일으켜비만치료제로서의가능성을기대했으나, 많은연구결과에서제2형당뇨질환환자와비만환자의경우혈중내높은농도로존재한다고알려졌고렙틴수용체의하향조절로인한렙틴저항성이발생되어체중감소효과를기대하기가어렵다. 일반적으로 o/o 마우스에서체중감소를위한증가된렙틴농도조절의실패를렙틴저항성이라고정의하는데, 렙틴수용체의감소는렙틴기능의결함과불완전한생리학적반응을유도하여렙틴저항성비만과제2형당뇨병의병인에있어서중요한역할을한다고알려져있다 (22,23). 본연구결과는혈중인슐린농도와렙틴농도와의상관관계를명확히보여주며렙틴이고인슐린증과인슐린저항성에있어서중요한역할을한다는이전연구결과를뒷받침하고있다 (24). 새싹추출물이제2형당뇨질환에있어서혈중인슐린과렙틴농도를현저하게감소시킴으로써렙틴저항성과인슐린저항성을개선시키고, 혈당조절과비만억제에효과가있는탁월한식품소재로서의가능성이 있음을제시한다. 요약본연구에서는고지방식이와 streptozotocin으로유도된제 2형당뇨마우스에서새싹추출물의항당뇨효과를살펴보았다. 제2형당뇨유도후 4주동안의체중변화를관찰한결과새싹추출물군과메트포민군에서유의한체중감소변화가나타났으며, 식이섭취량에따른변화는모든실험군간의차이가없었다. 공복혈당은고지방식이군의경우실험종료일까지지속적으로상승하였고, 이와대조적으로새싹추출물과메트포민군의경우실험 2주째부터감소하여실험종료 4주째에서는고지방식이군보다유의적으로감소하였다. 경구내당능검사는포도당섭취후 60분, 90분, 120분에서새싹추출물과메트포민군이고지방식이군보다유의적으로감소하였으며, 인슐린내성검사는 120분에서새싹추출물과메트포민군이고지방식이군보다유의성있게감소하였다. 혈중지질농도변화에서총콜레스테롤, 중성지방그리고 LDL 콜레스테롤농도는고지방식이군에비해새싹추출물과메트포민군에서유의적으로감소하였고, HDL 콜레스테롤농도는고지방식이군에비해새싹추출물과메트포민군에서증가하였다. 간독성의지표인 glutamate oxaloacetate transaminase와 glutamate pyruvate transaminase 효소활성도는메트포민투여군과고지방식이군을제외한실험군들간에유의성이나타나지않았다. 혈중인슐린과렙틴농도는고지방식이군에비해새싹추출물과메트포민군에서유의적으로감소하였다. 이상의결과를바탕으로새싹추출물은제2형당뇨마우스에서체중을감소시키고혈중지질대사이상을조절하면서인슐린저항성을감소시켜혈당을개선하므로항당뇨효과가있는우수한식품소재로서의개발가능성을시사하고있다.

7 1664 이현서 강현주 전인화 염정호 장선일 감사의글 이논문은 2013년도산학연협력기술개발사업 (C031) 으로중소기업청지원을받아연구되었다. REFERENCES 1. Park CM, Kwak BH, Sharma BR, Rhyu DY Anti-diaetic effect of Opuntia humifusa stem extract. Kor J Pharmacogn 43: Krentz AJ, Bailey CJ Oral antidiaetic agents: current role in type 2 diaetes mellitus. Drugs 65: Rondinone CM Diaetes: the latest developments in inhiitors, insulin sensitizers. Expert Opin Ther Target 9: Kadowaki T, Yamauchi T, Kuota N, Hara K, Ueki K, Toe K Adiponectin and adiponectin receptors in insulin resistance, diaetes, and the metaolic syndrome. J Clin Invest 116: Lee SH, Lim SL, Lee YM, Hur JM, Lee HS, Kim DK Anti-diaetic effects of Triticum aestivum L. water extracts in d/d mice as an animal model of diaetes mellitus type Ⅱ. Kor J Pharmacogn 41: Khalila AW, Ze A, Mahmood F, Tariq S, Khattak AB, Shaha H Comparison of sprout quality characteristics of desi and kauli type chickpea cultivars (Cicer arietinum L.). LWT-Food Sci Technol 40: Peroni DG, Bonomo B, Casarotto S, Boner AL, Piacentini GL How changes in nutrition have influenced the development of allergic diseases in childhood. Ital J Pediatr 38: 22: Kim HS, Jeon IH, Kang HJ, Mao X, Mok JY, Lee BS, Cheon CJ, Jang SI Antioxidant effects of ethanol extracts of ay vegetales. J Nat Sci 23: Hundal RS, Krssak M, Dufour S, Laurent D, Leon V, Chandramouli V, Inzucchi SE, Schumann WC, Petersen KF, Landau BR, Shulman GI Mechanism y which metformin reduces glucose production in type 2 diaetes. Diaetes 49: Zhou G, Myers R, Li Y, Chen Y, Shen X, Fenyk-Melody J, Wu M, Ventre J, Doeer T, Fujii N, Musi N, Hirshman MF, Goodyear LJ, Moller DE Role of AMP-activated protein kinase in mechanism of metformin action. J Clin Invest 8: Kim OK, Oak CH, Jeong JM, Lee JW, Shin MH, Kim NH A case of metformin-induced lactic acidosis with acute kidney injury misdiagnosed as hepatorenal syndrome in a cirrhosis patient. Korean J Med 82: Altun E, Kaya B, Paydaş S, Sarıakçalı B, Karayaylalı I Lactic acidosis induced y metformin in a chronic hemodialysis patient with diaetes mellitus type 2. Hemodial Int 18: Friedewald WT, Levy RI, Fredrickson DS Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 18: Reitman S, Frankel S A colorimetric method for the determination of serum glutamic oxalacetic and glutamic pyruvic transaminases. Am J Clin Pathol 28: Sunil C, Duraipandiyan V, Agastian P, Ignacimuthu S Antidiaetic effect of plumagin isolated from Plumago zeylanica L. root and its effect on GLUT4 translocation in streptozotocin-induced diaetic rats. Food Chem Toxicol 50: Woods SC, Seeley RJ, Rushing PA, D'Alessio D, Tso P A controlled high-fat diet induces an oese syndrome in rats. J Nutr 133: Cowley MA, Smith RG, Diano S, Tschöp M, Pronchuk N, Grove KL, Strasurger CJ, Bidlingmaier M, Esterman M, Heiman ML, Garcia-Segura LM, Nillni EA, Mendez P, Low MJ, Sotonyi P, Friedman JM, Liu H, Pinto S, Colmers WF, Cone RD, Horvath TL The distriution and mechanism of action of ghrelin in the CNS demonstrates a novel hypothalamic circuit regulating energy homeostasis. Neuron 37: Klok MD, Jakosdottir S, Drent ML The role of leptin and ghrelin in the regulation of food intake and ody weight in humans: a review. Oes Rev 8: Al-Shoumer KA, Al-Asousi AA, Doi SA, Vasanthy BA Serum leptin and its relationship with metaolic variales in Aras with type 2 diaetes mellitus. Ann Saudi Med 28: Myers MG, Cowley MA, Münzerg H Mechanisms of leptin action and leptin resistance. Annu Rev Physiol 70: Gilert ER, Fu Z, Liu D Development of a nongenetic mouse model of type 2 diaetes. Exp Diaetes Res 2011: Zhang S, Zhang Q, Zhang L, Li C, Jiang H Expression of ghrelin and leptin during the development of type 2 diaetes mellitus in a rat model. Mol Med Rep 7: Sahu A, Nguyen L, O'Doherty RM Nutritional regulation of hypothalamic leptin receptor gene expression is defective in diet-induced oesity. J Neuroendocrinol 14: Levin BE, Dunn-Meynell AA, Ricci MR, Cummings DE Anormalities of leptin and ghrelin regulation in oesity-prone juvenile rats. Am J Physiol Endocrinol Meta 285: E

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