Loss of plasma glucose lowering response to cold stress in opioid μ-receptor knock-out diabetic mice

Abstract

Opioid μ-receptor plays an important role in the regulation of glucose homeostasis in diabetic rats lacking insulin. Opioid μ-receptor knockout mice were employed to identify the essential role of this receptor in the present study. Western blotting analysis characterized the deletion of opioid μ-receptor in liver of knockout mice as compared to that of normal (wild-type) mice. We found that the plasma glucose concentration of diabetic mice induced by intraperitoneal injection of streptozotocin was markedly decreased after exposure to cold-stress in a cold room for 1 h. However, this plasma glucose lowering response to cold-stress was disappeared in diabetic mice lacking opioid μ-receptor. The important role of opioid μ-receptor in the plasma glucose lowering response to cold stress can thus be considered. Moreover, bilateral adrenalectomy abolished this plasma glucose lowering response to cold stress in diabetic mice with opioid μ-receptor, as compared to the shamed-operated animals. Therefore, activation of opioid μ-receptor by opioid from adrenal gland appears to be responsible for the plasma glucose lowering response to cold-stress in diabetic mice with insulin deficiency.