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Effects of Zinc Plus Arachidonic Acid on Insulin Resistance in High Fructose-Fed Rats

Zinc와 Arachidonic Acid가 고 Fructose 식이로 유도된 인슐린 저항성에 미치는 영향

  • 최철수 (가천의과학대학교) ;
  • 김영욱 (마산 삼성병원) ;
  • 이효선 (부산대학교 의학전문대학원) ;
  • 윤태호 (부산대학교 의학전문대학원) ;
  • 조병만 (부산대학교 의학전문대학원) ;
  • 이수일 (부산대학교 의학전문대학원) ;
  • 김성수 (부산대학교 의학전문대학원) ;
  • 황인경 (부산대학교 의학전문대학원)
  • Published : 2009.04.30

Abstract

We previously demonstrated that zinc plus arachidonic acid (ZA) treatment lowered blood glucose levels in streptozotocin-induced diabetic rats, genetically diabetic obese (ob/ob) mice, and genetically diabetic, non-obese Goto-Kakizaki rats. However, plasma insulin levels did not increase with ZA treatment, suggesting that ZA lowers blood glucose levels not by stimulating pancreatic insulin secretion. However, it is unclear whether these agents lower blood glucose levels by decreasing hepatic glucose output (HGO) or by increasing glucose utilization in peripheral tissues, or both. In order to determine ZA target organ of insulin action, we divided 18 Sprague-Dawley rats weighing ${\sim}130g$ into 3 groups (6 rats per group) and treated them for four weeks with: (1) Control diet (regular rat chow), (2) High fructose (60.0%) diet only, and (3) the same fructose diet plus zinc (10 mg/L) and arachidonic acid (50 mg/L) containing drinking water. After 4 weeks, insulin action was assessed using the hyperinsulinemic euglycemic clamp technique. Food intake and body weights were comparable in all three groups of rats throughout the study period. Plasma glucose and insulin concentrations, glucose uptake, and HGO in the basal state were all the same in these three rat groups. During the clamp study, fructose-treated and fructose+ZA treated rat groups did not exhibit any detectable change on insulin-mediated glucose uptake compared to controls. High fructose feeding impaired insulin mediated suppression of HGO, compared to controls during clamp (4.39 vs. 2.35 mg/kg/min; p<0.05). However, ZA treatment in high fructose-fed rats showed a remarkable increase in hepatic insulin sensitivity compared to high fructose-fed rats, reflected by a complete recovery in suppression of HGO during the clamp (4.39 vs. 2.18 mg/kg/min; p<0.05). This data suggests that ZA increases insulin sensitivity in liver but not glucose utilization of peripheral tissues in high fructose-fed rats.

고 fructose 식이를 섭취시켜 제 2형 당뇨를 유발한 쥐에서 ZA의 섭취가 혈당 조절에 미치는 기전을 밝히고자 하였다. 4주 동안의 실험기간 중 Control군(normal chow diet), Fructose군(high-fructose diet)과 Fructose+ZA군(highfructose diet+ZA treatment) 간의 체중, 먹이 및 물의 섭취량에는 유의한 차이를 나타내지 않았다(p<0.05). 기저상태 (basal state)에서 혈장 포도당, 인슐린 농도 및 간의 포도당 생성률을 측정한 결과 Control군과 Fructose군 및 Fructose+ZA군 간의 차이를 나타내지 않았다. 인슐린 감수성을 알아보기 위한 hyperinsulinemic euglycemic clamp 실험에서 인슐린 농도와 포도당 농도는 군 간의 차이를 나타내지 않았다. 또한 인슐린 감수성 지표인 포도당 흡수(glucose uptake)에서도 역시 군 간의 차이를 발견하지 못하였다. 그러나 간의 인슐린 감수성 지표인 간의 포도당 생성률(HGO)에서는 Fructose군이 Control군에 비하여 유의적으로 증가되었고 (p<0.05), Fructose+ZA군이 대조군의 수준으로 감소되었다. 이것으로 미루어 볼 때 fructose 식이는 간에서 인슐린감수성을 감소시켰으나 당뇨는 유발되지 않았으며, ZA 섭취가 간의 포도당 생성률을 억제하는 것으로 보아 인슐린 감수성을 증가시키지만, 말초조직의 포도당 이용에는 영향을 미치지 않는 것으로 사료된다.

Keywords

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