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The aim of this study is to investigate the effect of U50,488H, a selective κ-opioid receptor (κ-OR) agonist, on the blood glucose level in the streptozotocin-induced diabetic mice and the underlying mechanisms.Multiple low doses of streptozotocin (60 mg/kg, intraperitoneally for 3 consecutive days) were used to induce hyperglycemia in mice.The blood glucose was detected from the caudal vein after the administration of U50,488H (3 mg/kg, intravenously).