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


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.


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