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Loss of plasma glucose lowering response to cold stress in opioid mu-receptor knock-out diabetic mice
1Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan City, Taiwan, ROC.
Abstract:
Opioid mu-receptor plays an important role in the regulation of glucose homeostasis in diabetic rats lacking insulin. Opioid mu-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 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 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 mu-receptor. The important role of opioid mu-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 mu-receptor, as compared to the shamed-operated animals. Therefore, activation of opioid mu-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.
Insights
The opioid mu-receptor is crucial for lowering blood glucose in diabetic mice during cold stress. Its absence prevents this glucose-lowering effect, highlighting its role in metabolic regulation.
Area of Science:
- Endocrinology
- Neuroscience
- Metabolic Research
Background:
- Opioid mu-receptor involvement in glucose homeostasis is known.
- Insulin deficiency significantly impacts glucose regulation.
Purpose of the Study:
- To investigate the essential role of the opioid mu-receptor in glucose regulation.
- To determine the mechanism of cold-stress-induced glucose lowering in diabetic mice.
Main Methods:
- Utilized opioid mu-receptor knockout mice and streptozotocin-induced diabetes model.
- Performed Western blotting to confirm receptor deletion.
- Exposed mice to cold stress and measured plasma glucose levels.
- Conducted bilateral adrenalectomy to assess adrenal gland involvement.
Main Results:
- Diabetic mice showed decreased plasma glucose after cold stress.
- This glucose-lowering response was absent in diabetic mice lacking the opioid mu-receptor.
- Adrenalectomy abolished the glucose-lowering response in diabetic mice with the receptor.
Conclusions:
- Opioid mu-receptor is essential for the plasma glucose lowering response to cold stress in diabetic mice.
- Activation of the opioid mu-receptor by adrenal opioids mediates this response.
- Findings suggest a novel pathway for glucose regulation in insulin deficiency.
