• 제목/요약/키워드: plasma insulin

검색결과 458건 처리시간 0.037초

흰쥐에서 다족쇄 n-3 다불포화지방산이 콜라젠-유도 관절염의 발생에 미치는 영향 (The Effect of Long Chain n-3 Polyunsaturated Fatty Acids on Development of Collagen-induced Arthritis in Rats)

  • 신경호;김세동;전환진;장용찬;이석강
    • Journal of Yeungnam Medical Science
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    • 제19권1호
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    • pp.39-48
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    • 2002
  • n-3 불포화지방산이 관절염의 발생 및 경과에 미치는 영향에 대해 알아보고자 Louvain종 흰쥐를 사용하여, 실험군을 정상군과 면역유도 (콜라겐+incomplete Freund's adjuvant)군으로 나누었고, 면역유도군은 다시 대조군 (정상식이) 및 n-3 다불포화지방산군 (식이에 5% n-3 다불포화지방산 함유) 으로 구분하여, 관절염 유도 1 주일전부터 n-3 다불포화지방산이 함유된 식이를 섭취시켰으며 관절염의 발생여부를 x-ray 소견과 광학현미경적 관찰을 통하여 확인하였다. 면역유도 5 주에 대조군의 38%에서 x-ray 소견상 족부종과 광학현미경상 염증소견이 발견되었으나 n-3 다불포화군에서는 이러한 변화가 없었다. 혈당과 혈장 인슐린은 면역유도나 n-3 다불포화지방산 투여에 의한 변화가 없었으나 혈장 중성지방과 콜레스테롤은 n-3 다불포화지방산투여에 의하여 감소하였다. n-3 다불포화지방산의 투여가 콜라젠에 의한 관절염의 발생을 예방 또는 치료할 수 있을 것으로 생각되며 이의 작용기전을 설명하기 위하여 후속 연구가 요망된다.

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Effects of Astragalus Polysaccharides, Achyranthes bidentata Polysaccharides, and Acantbepanax senticosus Saponin on the Performance and Immunity in Weaned Pigs

  • Kang, P.;Xiao, H.L.;Hou, Y.Q.;Ding, B.Y.;Liu, Y.L.;Zhu, H.L.;Hu, Q.Z.;Hu, Y.;Yin, Y.L.
    • Asian-Australasian Journal of Animal Sciences
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    • 제23권6호
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    • pp.750-756
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    • 2010
  • Two trials were conducted to study the effects of two Chinese herbal polysaccharides, Astragalus polysaccharides (APS) and Achyranthes bidentata polysaccharides (ABPS), and one Chinese herbal saponin, Acantbepanax senticosus saponin (ASS), on the immunity and growth performance of weaned pigs. Experiment 1 was a 14-day growth assay, in which 32 weaned pigs were randomly allocated to one of four dietary treatments: i) 0.05% talcum powder control; ii) 0.05% APS; iii) 0.05% mixture of APS and ASS in a 1:1 ratio by weight; and iv) 0.05% mixture of APS, ASS, and ABPS in a ratio of 1:1:1 by weight. Blood samples were collected on day 14 to determine plasma parameters. Feed intake, body weight gain, and feed efficiency were also determined. Experiment 2 was a 21-day immunity assay, in which 16 weaned pigs were randomly allotted to one of two dietary treatments: i) 0.05% talcum powder control; and ii) 0.05% mixture of APS and ASS in a 1:1 ratio by weight. On day 21, pigs were challenged with lipopolysaccharide (LPS) and 3 h later blood samples were collected and analyzed for lymphocyte proliferation as well as interleukin 6 (IL-6), insulin-like growth factor 1 (IGF-1), growth hormone (GH), and cortisol levels. In Experiment 1, feeding Chinese herbal polysaccharides and saponin increased growth performance of the pigs. The effects of the mixture of APS and ASS were especially notable, as there was a significant improvement in growth performance compared with the control (p<0.05). The plasma concentration of immunoglobulin G (IgG), nitric oxide (NO), and nitric oxide synthase (NOS) were increased in all treatments groups, with the mixture of APS and ASS increasing the level of IgG and NOS significantly (p<0.05), compared with the control. There was no difference in the NO level between the control and treatment groups (p>0.05). In Experiment 2, Chinese herbal polysaccharides and saponin showed immunostimulating effects. The level of cortisol, GH, and IGF-I were significantly increased (p>0.05), and the level of IL-6 showed a significant decrease (p<0.05) in the APS and ASS treatment after the LPS challenge. The mixture of APS and ASS could stimulate the blood lymphocyte proliferation significantly whether the LPS was injected or not (p<0.05). These results show that Chinese herbal extracts can improve growth performance and stimulate immunity of weaned pigs. A mixture of APS and ASS, compared with APS alone, could be a new kind of immunostimulant for weaned pigs, which could result in greater positive effects on their growth performance and immunity.

소맥엽의 섭취가 Streptozotocin 유발 당뇨 흰쥐에서 혈중 포도당 및 지질에 미치는 영향 (Effects of Triticum aestivum sprout on Blood Glucose and Lipid Levels in the Streptozotocin-Induced Diabetic Mice)

  • 이선희;임성원;이영미;강천식;정연근;박철수;송봉준;김대기
    • 동의생리병리학회지
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    • 제24권6호
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    • pp.1012-1018
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    • 2010
  • This study investigated the functional effect by diets of Triticum aestivum sprout (TA) on the levels of blood glucose and lipid profiles in streptozotocin(STZ)-induced diabetic mice. Diabetes mellitus were induced by STZ intraperitoneal injection (50 mg/kg) into the male Balb/c mice. All mice fed AIN-93 diet for 3 weeks. Mice were divided to 4 groups: normal, diabetic control and two experimental groups (TA 5.0, diet with Triticum aestivum sprout 5.0% w/w; TA 2.5, diet with Triticum aestivum 2.5% w/w). The blood glucose level was decreased by TA intake in diabetic mice in the dose-dependant manner; 21.34% and 35.77% in TA 2.5 and TA 5.0 groups. The weight gain and feed efficiency ratio also were improved by TA intake compared with DM group. The weight gain was increased 1.28 and 1.09 folds in TA 5.0 and TA 2.5 groups, respectively. The weight of organs, including liver and kidney, was reduced but that of spleen and abdominal fat was increased by TA intake. Moreover, TA treatment increased the level of HDL but decreased the level of total cholesterol and triglycerides in the blood of diabetic mice. The blood of HbA1c also was significantly decreased without changing hematocrit by TA treatment compared with DM group. These results indicate the TA intake has the functional effects attenuating blood glucose and plasma lipid levels in insulin-dependent diabetes.

과체중 및 비만 여성에서 의학영양치료에 의한 체격지수의 변화 양상 및 식사 섭취와 혈액학적 지표의 변화 (Effects of Medical Nutrition Therapy on Changes of Anthropometric Measurements, Dietary Pattern and Blood Parameters in Over Weight or Obese Women)

  • 이정숙;이혜옥;임정은;김영설;조여원
    • Journal of Nutrition and Health
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    • 제38권6호
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    • pp.432-444
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    • 2005
  • The purpose of this study was to investigate the effect of medical nutrition therapy (MNT) on anthropometric measurements, quality of diets, and blood parameters through the weight loss program in over weight or obese women. The subjects (n=76, $age\;31.1{\pm}8.4y,\;weight\;70.3{\pm}7.9kg,\;BMI\;27.2{\pm}2.4kg/m^2$) without medical disease were treated with MNT 5 times for 12 weeks by dietitian. Anthropometric measurements included height, weight, fat mass, lean body mass, triceps and thigh skin-fold thickness, mid-arm, waist, hip and thigh circumference. Dietary assessments were accomplished using 3-days food records, diet quality index (DQI), and dietary pattern. The dietary pattern was assessed by daily energy intakes from breakfast, lunch, dinner, and snacks of calorie density, and numbers of eating. Blood levels of leptin, lipid profiles (total lipids, total cholesterol, LDL-cholesterol, HDL-cholesterol), and insulin were analyzed. Anthropometric measurements decreased significantly after MNT (p<0.001). Waist circumference was reduced most rapidly and tricep skin-fold thickness was reduced most effectively after 12 weeks of MNT. Daily energy intake, calorie density and numbers of eating incidence decreased significantly $0796.4{\pm}395.5\;vs\;1402.9{\pm}217.8\;kcal/day,\;162.3{\pm}56.5\;vs\;113.4{\pm}30.1,\;5.0{\pm}1.4\;vs\;3.8{\pm}0.4$, respectively, p<0.05). The daily energy intake from breakfast and snacks significantly decreased (p<0.001). Calories from snack, calorie density of snack and numbers of snacking also decreased (p<0.05). The mean scores of DQI significantly increased ($7.6{\pm}2.1\;vs\;6.5{\pm}1.6$, p<0.05). The plasma levels of total lipid, triglyceride (TG), total cholesterol, LDL-cholesterol and leptin decreased significantly after MNT ($489.8{\pm}100.4\;vs\;447.0{\pm}87.3mg/dL,\;187.7{\pm}34.0\;vs\;175.9{\pm}31.5mg/dL,\;115.2{\pm}29.2\;vs\;109.2{\pm}26.7mg/dL,\;15.7{\pm}7.6\;vs\;12.4{\pm}5.9ng/mL$, respectively, p<0.05). These results indicate that MNT efficiently reduced the body weight through the changes in dietary intake, dietary patterns and dietary quality. MNT also changed body composition and reduced the levels of plasma lipid, cholesterol and leptin.

고지방식이를 급여한 C57BL/6J 마우스에서 상지추출물과 스틸벤 화합물의 항비만 효능 연구 (Anti-obesity effect of Ramulus mori extracts and stilbenes in high fat dietfed C57BL/6J mouse)

  • 박정은;이건희;김주희;최상원;김은정
    • Journal of Nutrition and Health
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    • 제53권6호
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    • pp.570-582
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    • 2020
  • 본 연구는 상지추출물과 stilbene 화합물인 MSA, ORT의 항비만 효능을 비교 분석하고자 식이성 비만 마우스 모델을 이용하여 HFD에 실험물질을 첨가한 식이를 13주 동안 급여하였다. 연구결과, 실험물질들의 항비만 효능은 ORT, ME, MSA, MW군 순이었으며, 특히 ME와 ORT의 급여는 고지방식이에 의한 체중 및 체지방 증가, 혈당 증가, 이상지질혈증 및 지방간 개선에 있어 양성대조군인 GC군과 비슷한 효과를 보였다. 향후 관련 기작 규명 및 안전성 확보, 그리고 최대 유효성 도출을 위한 추출 조건 확립 및 용량 검증 등의 연구가 수행된다면 체중조절용 기능성 식품으로의 개발을 기대해 볼 수 있을 것으로 사료된다.

Effects of protein content and the inclusion of protein sources with different amino acid release dynamics on the nitrogen utilization of weaned piglets

  • Hu, Nianzhi;Shen, Zhiwen;Pan, Li;Qin, Guixin;Zhao, Yuan;Bao, Nan
    • Animal Bioscience
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    • 제35권2호
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    • pp.260-271
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    • 2022
  • Objective: We aimed to investigate the effect of the differing amino acid (AA) release dynamics of two protein sources on the growth performance, nitrogen deposition, plasma biochemical parameters, and muscle synthesis and degradation of piglets when included in their diets at normal and low concentrations. Methods: Forty-eight piglets (Duroc×Landrace×Large White) with initial body weight of 7.45±0.58 kg were assigned to six groups and fed one of 6 diets. The 6 dietary treatments were arranged by 3×2 factorial with 3 protein sources and 2 dietary protein levels. They are NCAS (a normal protein content with casein), NBlend (a normal protein content with blend of casein and corn gluten meal), NCGM (a normal protein content with corn gluten meal), LCAS (a low protein content with casein), LBlend (a low protein content with blend of casein and corn gluten meal), LCGM (a low protein content with corn gluten meal). The release dynamics of AA in these diets were determined by in vitro digestion. The digestibility, utilization and biological value of nitrogen in piglets were determined by micro Kjeldahl method. Plasma insulin was measured by enzyme-linked immunosorbent assay kits. The protein expression of mediators of muscle synthesis and degradation was determined by western blotting. Results: Although the consumption of a low-protein diet supplemented with crystalline AA was associated with greater nitrogen digestion and utilization (p<0.05), the final body weight, growth performance, nitrogen deposition, and phosphorylation of ribosomal protein S6 kinase 1 and eIF4E binding protein 1 in the muscle of pigs in the low-protein diet-fed groups were lower than those of the normal-protein diet-fed groups (p<0.05) because of the absence of non-essential AA. Because of the more balanced release of AA, the casein (CAS) and Blend-fed groups showed superior growth performance, final body weight and nitrogen deposition, and lower expression of muscle ring finger 1 and muscle atrophy F-box than the CGM-fed groups (p<0.05). Conclusion: We conclude that the balanced release of AA from CAS containing diets and mixed diets could reduce muscle degradation, favor nitrogen retention, % intake and improve growth performance in pigs consuming either a normal- or low-protein diet.

Streptozotocin 유도 당뇨 마우스에서 상지 물추출물의 이당류 분해효소활성 억제를 통한 항당뇨 효능 (Antidiabetic effects of water extracts of mulberry (Morus alba L.) twig by inhibition of disaccharidase activity in streptozotocin-induced diabetic mice)

  • 안은영;신수진;최상원;김은정
    • Journal of Nutrition and Health
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    • 제56권1호
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    • pp.24-34
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    • 2023
  • 상지 물추출물의 투여는 STZ 유도 당뇨 마우스의 공복 혈당, 혈중 총 CHO, LDL-CHO, 간 무게 및 간 조직 TG를 NC군 수준으로 감소시키고 혈장 총 CHO대비 HDL-CHO비는 NC군 수준으로 증가시켰으며, 소장 proximal region의 이당류 분해효소인 lactase, sucrase 활성을 억제하였다. 이는 상지를 차로 우려내어 음용할 경우 당뇨 예방 및 증상 개선의 가능성을 기대해 볼 수 있음을 제시한다. 상지는 국내산 뽕나무 부산물로 대량 생산될 뿐만 아니라 식품의 원료로 사용이 가능한 소재이므로 향후 상지 물추출물의 생리활성성분 분리 및 혈당조절기전 연구를 보다 깊이 수행한다면 안전하고 효과적인 고부가가치 혈당조절 기능성식품 개발의 기초자료로 활용될 수 있을 것이다.

손바닥선인장의 열매와 줄기가 Streptozotocin으로 유발된 당뇨 쥐의 혈당 및 지질대사에 미치는 영향 (Effects of Fruits and Stems of Opuntia ficus-indica on Blood Glucose and Lipid Metabolism in Streptozotocin-induced Diabetic Rats)

  • 윤진아;손용석
    • 한국식품영양과학회지
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    • 제38권2호
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    • pp.146-153
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    • 2009
  • 손바닥선인장의 항당뇨 효과와 기작을 알아보기 위한 연구의 일환으로, 손바닥선인장의 열매 및 줄기의 급여가 STZ으로 당뇨가 유발된 8주령 수컷 흰쥐의 음수량, 식이섭취량, 체중, 공복혈당, 당내성에 미치는 효과와 당뇨의 합병증인 고지혈증(중성지방, 유리지방산, 총콜레스테롤, LDL-콜레스테롤, HDL-콜레스테롤)을 조사하였다. 손바닥선인장의 열매 및 줄기는 동결건조 후 분쇄하여 분말사료에 8%(열매) 및 5%와 10%(줄기) 수준으로 첨가하여 3주간 자유채식 시켰다. 실험군은 정상군(NC), 당뇨대조군(DC), 열매급여군 (DOF), 줄기5%급여군(DO-5), 줄기10%급여군(DO-10)으로 구분하였으며, 음수량은 1일, 식이섭취량은 2일 간격, 체중 및 혈당은 1주 간격으로 측정하였는데, 혈당은 12시간 절식 후 꼬리정맥에서 측정하였다. 당 내성은 공복 시 혈당을 측정한 후 포도당(50 mg/체중 1 kg)을 복강에 주사한 다음, 30, 60, 90, 120분 경과하였을 때 혈당과 동일한 방법으로 측정하였다. 수분함량은 열매가 94.5%, 줄기가 92.3%였고, 조회분, 조단백, 조지방, 조섬유 등의 농도는 줄기가 열매에 비해 높았고, NFE는 열매가 줄기에 비해 높았다. 체중변화는 DC에 비해 DOF에서 체중이 적게 감소했다. 음수량과 사료섭취량은 NC에 비해 DC가 각각 7.5배 및 1.5배 이상 증가하였고, 처리군들은 음수량 및 식이섭취량이 DC에 비해 낮았다. NC의 공복혈당은 평균 100 mg/dL이었고 DC는 379 mg/dL이었으며, DOF는 DC에 비해 28%의 혈당 감소를 보인 반면(P<0.05), DO-5는 5%와 DO-10은 9% 감소하여 유의적 차이를 보이지 않았다. 당 내성 실험에서 NC와 DO-5는 급여한지 30분 후에, 다른 처리군은 60분 후에 최고 혈당을 나타내었다. 혈장 인슐린 함량도 당뇨대조군과 비교해 DOF, DO-5와 DO-10에서 유의적(p<0.05)인 증가를 보였다. 이로써 손바닥선인장의 열매가 STZ으로 당뇨가 유발된 쥐에서 당뇨의 개선효과가 있는 것으로 판단된다. 또한 손바닥선인장의 열매 및 줄기 모두 당뇨의 합병증인 지질대사에서 혈장의 중성지방, 유리지방산, 총 콜레스테롤 그리고 LDL-콜레스테롤을 모두 DC와 비교해 DOF, DO-5와 DO-10에서 유의적인 감소를 보였다(p<0.05). 이상의 결과에서 볼 때, 손바닥선인장의 열매는 항당뇨효능이 있었고, 또 당뇨 합병증인 지질대사의 이상도 개선하는 것으로 관찰되었으며, 그 줄기는 통계적으로 유의한 혈당감소 효과를 보이지는 않았지만 당뇨의 합병증인 고지혈증을 개선시키는 것으로 나타나, 보다 구체적인 작용기작을 추가적 연구를 통해 확인할 필요가 있다고 사료된다.

Insulin-like growth factor가 소장 점막 세포 증식에 미치는 영향

  • 윤정한
    • 한국영양학회:학술대회논문집
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    • 한국영양학회 1995년도 추계학술대회 초록
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    • pp.11-34
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    • 1995
  • Growth hormone (GH) plays a key role in regulating postnatal growth and can stimulate growth of animals by acting directly on specific receptors on the plasma membrane of tissues or indirectly through stimulating insulin-like growth factor (IGF)-I synthesis and secretion by the liver and other tissues. IGF-I and IGF-Ⅱ are polypeptides with structural similarity with proinsulin that stimulate cell proliferation by endocrine, paracrine and autocrine mechanisms. The initial event in the metabolic action of IGFs on target cells appears to be their binding to specific receptors on the plasma membrane. Current evidence indicates that the mitogenic actions of both IGFs are mediated primarily by binding to the type I IGF receptors, and that IGF action is also mediated by interactions with IGF-binding proteins (IGFBPs). Six distinct IGFBPs have been identified that are characterized by cell-specific interaction, transcriptional and post-translational regulation by many different effectors, and the ability to either potentiate or inhibit IGF actions. Nutritional deficiencies can have their devastating consequence during growth. Although IGF-I is the major mediator of GH's action on somatic growth, nutritional status of an organism is a critical regulator of IGF-I and IGFBPs. Various nutrient deficiencies result in decreased serum IGF-I levels and altered IGFBP levels, but the blood levels of GH are generally unchanged or elevated in malnutrition. Effects of protein, energy, vitamin C and D, and zinc on serum IGF and IGFBP levels and tissue mRNA levels were reviewed in the text. Multiple factors are involved in the regulation of intestinal epithelial cell growth and differentiation. Among these factors the nutritional status of individuals is the most important. The intestinal epithelium is an important site for mitogenic action of the IGFs in vivo, with exogenous IGF-I stimulating mucosal hyperplasia. Therefore, the IGF system appears to provide and important mechanism linking nutrition and the proliferation of intestinal epithelial cells. In order to study the detailed mechanisms by which intestinal mucosa is regulated, we have utilized IEC-6 cells, an intestinal epithelial cell line and Caco-2 cells, a human colon adenocarcinoma cell line. Like intestinal crypt cells analyzed in vivo or freshly isolated intestinal epithelial cells, IEC-6 cells and Caco-2 cells possess abundant quatities of both type Ⅰ and type Ⅱ IGF receptors. Exogenous IGFs stimulate, whereas addition of IGFBP-2 inhibits IEC-6 cell proliferation. To investigate whether endogenously secreted IGFBP-2 inhibit proliferation, IEC-6 cells were transfected with a full-length rat IGFBP-2 cDNA anti-sense expression construct. IEC-6 cells transfected with anti-sense IGFBP-2 protein in medium. These cells grew at a rate faster than the control cells indicating that endogenous IGFBP-2 inhibits proliferation of IEC-6 cells, probably by sequestering IGFs. IEC-6 cells express many characteristics of enterocyte, but do not undergo differentiation. On the other hand, Caco-2 cells undergo a spontaneous enterocyte differentiation. On the other hand, Caco-2 cells undergo a spontaneous enterocyte differentiation after reaching confluency. We have demonstrated that Caco-2 cells produce IGF-Ⅱ, IGFBP-2, IGFBP-3, and an as yet unidentified 31,000 Mr IGFBP, and that both mRNA and peptide secretion of IGFBP-2 and IGFBP-3 increased, but IGFBP-4 mRNA and protein secretion decreased after the cells reached confluency. These changes occurred in parallel to and were coincident with differentiation of the cells, as measured by expression of sucrase-isomaltase. In addition, Caco-2 cell clones forced to overexpress IGFBP-4 by transfection with a rat IGFBP-4 cDNA construct exhibited a significantly slower growth rate under serum-free conditions and had increased expression of sucrase-isomaltase compared with vector control cells. These results indicate that IGFBP-4 inhibits proliferation and stimulates differentiation of Caco-2 cells, probably by inhibiting the mitogenic actions of IGFs.

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손바닥선인장 복합물이 당뇨 쥐의 혈당 및 지질대사에 미치는 영향 (Effects of Opuntia ficus-indica Complexes B(OCB) on Blood Glucose and Lipid Metabolism in Streptozotocin-induced Diabetic Rats)

  • 윤진아;손용석
    • 한국식품영양학회지
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    • 제22권1호
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    • pp.48-56
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    • 2009
  • 손바닥선인장 복합물(OCB)의 항당뇨 효과 및 기작을 알아보기 위한 연구의 일환으로, OCB의 급여가 STZ으로 당뇨가 유발된 8주령 수컷 흰쥐의 음수량, 식이 섭취량, 체중, 공복혈당, 당내성에 미치는 효과와 당뇨의 합병증인 고지혈증(중성지방, 유리 지방산, 총 콜레스테롤, LDL-콜레스테롤, VLDL-콜레스테롤, HDL-콜레스테롤)의 개선효과를 조사하였다. OCB는 손바닥선인장의 줄기, 여주, 천화분, 목단피, 산약, 강황과 호로파를 조합하여 제조하였고, 기본사료에 2%와 5%의 수준으로 첨가하여 8주령 rat 수컷에게 3주간 자유 채식시켰다. OCB의 수분함량 약 12%, 조회분 15.4%, 조지방 1.26%, 조단백질 4.9%, 조섬유량 6.3% 및 탄수화물 함량은 60% 이상으로 주성분은 탄수화물이었다. 체중은 NC에 비해 DC, OCB-2와 OCB-5에서 감소하였다. 음수량과 사료섭취량은 NC에 비해 DC가 각각 약 8배 및 1. 5배 이상 증가하였고, OCB-2와 OCB-5는 DC와 비교해 유의적 차이가 없었다. NC의 공복 혈당은 평균 100 $mg/d{\ell}$, DC는 416 $mg/d{\ell}$이었으며, OCB-2는 362 $mg/d{\ell}$, 그리고 OCB-5는 329 $mg/d{\ell}$로 혈당농도의 감소를 보였다. 당내성 실험에서 모든 실험군은 포도당을 급여한지 30분 후에 최고 혈당을 나타냈고, OCB-5는 유의적인 감소를 보였다(p<0.05). 혈장 인슐린 함량도 DC와 비교해 NC, OCB-2, 그리고 OCB-5에서 유의적인 증가를 보였다(p<0.05). 이상의 결과에서 OCB의 급여는 STZ으로 당뇨가 유발된 쥐에서 당뇨의 개선효과가 있는 것으로 판단된다. 또한, OCB의 급여는 당뇨의 합병증인 지질대사에서 혈장의 중성지방, 유리지방산, 총콜레스테롤, LDL-콜레스테롤 그리고 VLDL-콜레스테롤을 모두 DC와 비교해 유의적인 수준으로 감소시켰다(p<0.05). 이러한 결과에서 볼 때, OCB의 급여는 당뇨의 합병증인 지질대사의 이상도 개선하는 것으로 관찰되었다.