| Summary: | Trans-resveratrol (RES), a well-known polyphenol exerts various health-promoting benefits, including glucose homeostasis maintenance. Here, we have investigated the impact of insulin resistance (IR) on RES disposition. Rats were fed with 10%-fructose-water for 8 weeks for developing IR. The systemic exposure to RES significantly decreased (IR vs normal, AUC0-24h, 1.73, 3.79, 9.27 vs 2.50, 6.12, 12.6 μM∙h, 20, 50, 100 mg/kg, p < 0.05). Tissue exposures to RES and conjugates were significantly decreased. The accumulated amount of RES in urine of IR rats was significantly increased (IR vs normal, 44.1 vs 21.5 μmol). The expression of UDP-glucuronosyltransferases (UGT1a1, 1a6) was significantly up-regulated, whereas that of sulfotransferases (SULT1a1, 1a2, 1a3) was down-regulated in specific tissues. Down-regulation of specific transporters (MRP2, BCRP, OATP1b2, OAT1, OAT3) might alter RES pharmacokinetics. The altered pharmacokinetic behavior of RES was largely attributed to its higher urinary excretion in IR rats. Specific strategies are required for compensating these metabolic alterations.
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