초록 ▼

본 연구의 최종 목표는 인체에 안전하고 효과 있는 새로운 혈당강하제의 개발이다. 이전의 연구에서 Zinc plus Arachidonic Acid (AA)는 여러 가지 animal models에서 그 효과를 나타내었다. 그러므로 본 연구는 high fructose-fed rats에서 발생된 insulin-resistance에 대한 Zinc plus AA (ZA)의 효과와 안전성을 관찰하고 그 작용기전을 추정하고자 하였다.
Male Sprague-Dawley rat을 각각 6마리씩 3군으로 구분하여 1) Control군 : Nor

본 연구의 최종 목표는 인체에 안전하고 효과 있는 새로운 혈당강하제의 개발이다. 이전의 연구에서 Zinc plus Arachidonic Acid (AA)는 여러 가지 animal models에서 그 효과를 나타내었다. 그러므로 본 연구는 high fructose-fed rats에서 발생된 insulin-resistance에 대한 Zinc plus AA (ZA)의 효과와 안전성을 관찰하고 그 작용기전을 추정하고자 하였다.
Male Sprague-Dawley rat을 각각 6마리씩 3군으로 구분하여 1) Control군 : Normal chow diet 와 distilled water (DW) 2) Fructose 군 : high-fructose diet (HFD) 와 DW 3)FRuctose+ZA군 : HFD와 10 mg zinc, 0.5 mg L-histidine plus 50mg AA/L drinking water를 4주간 공급하였다. 4주간의 treatment 후 a)Hyperinsulinemic euglycemic clamp study: fructose feeding 에 의해 유발된 인슐린저항성에 미치는 ZA의 효과를 정량적으로 측정하고 그 작용기전을 추정하기 위하여 인슐린 감수성 지표들을 측정하고 비교, 분석하였다. b)혈액과 조직에서의 Zn 농도 측정: AA에 의하여 Zn의 이용도(bioavailability)가 향상되었는지를 평가하기 위하여 혈액과 간, 지방, 근육 조직에서 Zn 농도를 측정하였다. c) 안전성 평가: 체중 변화, 과도한 혈당저하 유무를 관찰하고, lipid profile, liver와 kidney 기능 등 biochemical marker 를 혈액에서 측정하였으며, Zn 사용으로 인한 Cu의 흡수 장애를 평가하기 위하여 혈액과 상기와 같은 조직에서 Cu의 농도를 측정하였다.

Abstract ▼

The major goal of the proposed studies are to develop a new anti-hyperglycemic agent, which are very effective and yet safe to use for the treatment of human diabetes. In our previous studies, Zinc plus Arachidonic acid (AA)(ZA) exhibited strong anti-diabetes activities in animal models. The specifi

The major goal of the proposed studies are to develop a new anti-hyperglycemic agent, which are very effective and yet safe to use for the treatment of human diabetes. In our previous studies, Zinc plus Arachidonic acid (AA)(ZA) exhibited strong anti-diabetes activities in animal models. The specific objectives in this proposal are to determine efficacy, safety and mechanism of using this new agent in fructose-induced insulin resistance. Male Sprague-Dawley rat will be treated for 4 weeks with 1) normal chow diet and distilled water (DW) 2) High-fructose diet (HFD) and DW 3) HFD and 10 mg zinc, 0.5 mg L-histidine plus 50 mg AA/L drinking water. To establish efficacy, safety, and mechanism of ZA in improvement of insulin-resistance in high fructose-fed rat, we conducted a) Hyperinsulinemic euglycemic clamp study: Effects of ZA on hepatic glucose output(HGO) and peripheral glucose utilizaion in the basal state of high fructose-fed rats were determined. And effects of ZA on insulin action to suppress HGO and to promote peripheral glucose utiization were determined in the presence of th maximum physiologic levels of plasma insulin b) Meaurement of Zn concentrations in blood or tissues: Whole blood, liver, fat, and muscle tissues were taken at the end of glucose calmp study to determine the enhancement of AA on zinc bioavailabilities in blood or tissues. c) Safety test: Toxicological outcomes were assessed by measuring enzymes and proteins related to liver and kidney functions, lipid profile, body weight change, possible hypoglycemia, or copper deficiency. Glucose uptake in rats treated with high-fructose diet for 4 weeks did not significantly decreased compared to normal chow fed rats in hyperinsulinemic euglycemic clamp study. During clamp, HGO of the normal chow fed rats was more supressed than the fructose-fed rats, and the effects of high-fructose feeding on HGO was prevented by the concomitant administration of ZA. But there were no statistically significant differences between two groups. We did not observed any adverse effects from treatment with ZA on body weight change, possible hypoglycemia, liver and kidney function, Cu deficiency in rats. We determined that ZA are safe to use in animals. ZA are found in most food and human organs, and finding any toxicities of these agents is remote. We have observed anti-hyperglycemic effects in several animal studies. Thus, We expect that this study will eventually lead toward development of a major anti-hypoglycemic agent that can treat millions of diabetic patient.

목차 Contents

• Ⅰ. 연구계획 요약문...3
• 1. 국문요약문...3
• Ⅱ. 연구결과 요약문...4
• 1. 국문요약문...4
• 2. 영문요약문...5
• Ⅲ. 연구내용...6
• 1. 서론...6
• 2. 연구방법 및 이론...7
• 3. 결과 및 고찰...10
• 4. 결론...17
• 5. 인용문헌...17