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OLETF 쥐에서 PPAR alpha agonist 투여에 의한 혈당치 및 췌장의 조직학적 변화에 관한 연구 원문보기
(The) effect of PPAR alpha agonist on the plasma glucose level and histologic change of pancreatic tissue in OLETF rat

  • 저자

    정석환

  • 학위수여기관

    東亞大學校 大學院

  • 학위구분

    국내석사

  • 학과

    의학과

  • 지도교수

  • 발행년도

    2001

  • 총페이지

    24p.

  • 키워드

    OLETF PPAR lpha agonist 혈당치 췌장;

  • 언어

    kor

  • 원문 URL

    http://www.riss.kr/link?id=T10067420&outLink=K  

  • 초록

    본 연구는 유전적으로 비만과 당뇨가 발생하는 동물 모델로서 사람에서의 비만형 당뇨병과 가장 유사한 동물 모델의 하나로 인정되고 있는 OLETF 쥐에서 당과 지질 대사의 중요한 조절인자인 핵내 수용체 Peroxisome proliferator activator receptor (PPAR) alpha agonist인 micronized fenofibrate가 혈당 및 췌장 조직의 형태학적 변화에 미치는 영향을 알아보고자 하였다. 33주령의 OLETF 쥐 20 마리를 2군으로 나누어 약물 투여군(10마리)은 micronized fenofibrate (100mg/㎏)를 백서용 분말 사료에 섞어서 투여하였고, 대조군(10마리)은 분말사료만 투여하였다. 8주간의 약물 투여 이후 인슐린 저항성을 알아보기 위해 정맥 당내성 검사 (intravenous glucose tolerance test, IVGTT)를 시행하면서 혈중 인슐린 및 혈당 농도의 변화를 살펴보고 homeostasis model assessment insulin resistance(HOMA-IR) index를 구하였다. 약물 투여 8주째 실험동물들을 모두 희생시킨 다음 췌장 조직을 적출하여 조직검사를 시행하였다. 실험 결과 대조군에서는 1.8% 체중증가를 보인 반면 약물 투여군에서는 10.5% 체중 감소를 보여 통계적으로 유의한 차이를 보였다 (P


    It is known that chronic increased concentration of free fatty acid inhibits insulin release and can cause insulin resistance. Fenofibrate is an agonist of peroxisome proliferator activated receptor (PPAR) alpha. The present study was peformed to determine whether PPAR alpha agonist improve insulin sensitivity and affect the morphological change of pancreatic tissue. We use micronized fenofibrate as PPAR alpha agonist and OLETF rat as the model of insulin resistance and type 2 diabetes. Twenty OLETF rats (33 week-aged) were divided to drug administration group (n=10) and control group (n=10). Micronized fenofibrate (as fenofibrate 100 mg/kg) was fed with chow food in drug administration group for 8 weeks. Fenofibrate treatment tended to decrease the intake of food and decreased the bodyweight significantly. In intravenous glucose tolerance test (IVGTT), the concentrations of insulin, the area under the curve (AUC) of insulin and homeostasis model assessment insulin resistance (HOMA-IR) index were lower in treatment group than those of control group. The concentration of glucose and the AUC of glucose during IVGTT were not different between two groups. In the histologic examination of pancreatic tissue, the islets were disorganized and islet cells were irregularly arranged. Fibrosis was prominent in the islets and the distances between affected islets were shortened. It means that loss and/or atrophy of exocrine tissue was severe. The islets were disrupted by fibrous strands and clustering of islets cells. These changes of the pancreas were less severe in treatment group than in control group. And there is considerable fatty changes within the pancreatic tissue in control group but little in treatment group. These results indicate that the administered micronized fenofibrate as a PPAR α agonist improve insulin resistance and obesity and also has some beneficial effect on the prevention of the destructive change of pancreatic tissue without influence on blood glucose concentration in OLETF rat.


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