Activation of κ-Opioid Receptor Exerts the Glucose-Homeostatic Effect in Streptozotocin-Induced Diabetic Mice

Opioid and its receptors play important roles in glucose homeostasis. However, few reports were available for the study of kappa-opioid receptor in glucose regulation. In our study, we found that the blood glucose of diabetic mice dropped significantly following the treatment with U50,488H (a selective kappa-opioid receptor agonist). This phenomenon was time-dependent and associated with the coincident alteration of Glut4 translocation in the skeleton muscles. U50,488H increased the serum adiponectin, but not serum insulin in diabetic mice. U50,488H increased the AdipoR1 expression at both mRNA and protein levels. It also promoted AMPK phosphorylation and Glut4 translocation. All these effects were abolished by nor-BNI (a selective kappa-opioid receptor antagonist). These findings suggest that activation of kappa-opioid receptor reduces hyperglycemia in streptozotocin-induced diabetic mice. This effect is associated with the translocation of Glut4 and might be relevant to increased adiponectin, AdipoR1, and AMPK phosphorylation. (C) 2014 Wiley Periodicals, Inc.