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

Opioid mu -receptor plays an important role in the regulation of glucose ho meostasis in diabetic rats lacking insulin. Opioid mu -receptor knockout mi ce were employed to identify the essential role of this receptor in the pre sent study. Western blotting analysis characterized the deletion of opioid mu -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 decrea sed after exposure to cold-stress in a cold room for 1 h. However, this pla sma glucose lowering response to cold-stress was disappeared in diabetic mi ce lacking opioid mu -receptor. The important role of opioid mu -receptor i n the plasma glucose lowering response to cold stress can thus be considere d. Moreover, bilateral adrenalectomy abolished this plasma glucose lowering response to cold stress in diabetic mice with opioid mu -receptor, as comp ared to the shamed-operated animals. Therefore, activation of opioid mu -re ceptor by opioid from adrenal gland appears to be responsible for the plasm a glucose lowering response to cold-stress in diabetic mice with insulin de ficiency. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.