Different roles of zinc plus arachidonic acid on insulin sensitivity between high fructose- and high fat-fed rats

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AimsThis study was to determine the effects of zinc plus arachidonic acid (ZA) treatment on the insulin action in the specific ZA target organs using hyperinsulinemic euglycemic clamp method. Main methods18 Sprague–Dawley rats weighing ~130g were divided into 3 groups of 6 rats and treated them with 1) normal rat chow, 2) high fructose (60.0%) diet only, or 3) the same fructose diet plus drinking water containing 10mg zinc plus 50mg arachidonic acid (AA)/L. In a separate study, male Wistar rats weighing ~250g were fed normal rat chow (n=4) or high fat (66.5%) diet with drinking water containing zero (n=9) or 10mg AA plus 20mg zinc /L (n=9). After 4week treatment, insulin action was assessed using the hyperinsulinemic eguglycemic clamp technique. Key findingsHigh fructose feeding impaired suppression of hepatic glucose output by insulin compared to controls during the clamp procedure (4.39 vs. 2.35mg/kg/min; p<0.05). However, ZA treatment in high fructose-fed rats showed a significant improvement of hepatic insulin sensitivity compared to non-treatment controls (4.39 vs. 2.18mg/kg/min; p<0.05). Glucose infusion rates in Wistar rats maintained on a high fat diet (HFD) were significantly lower compared to control rats (22.8±1.3 vs. 31.9±1.4mg/kg/min; p<0.05). ZA treatment significantly improved (~43%) peripheral tissue insulin sensitivity in HFD fed animals (26.7±1.3 [n=9] vs. 22.8±1.3mg/kg/min; p<0.05). SignificanceThese data demonstrate that ZA treatment is effective in improving glucose utilization in hyperglycemic rats receiving either a high-fructose or a high-fat diet.