Reduction of blood glucose level by orexins in fasting normal and streptozotocin-diabetic mice

Orexin-A and orexin-B are neuropeptides implicated in the maintenance of energy homeostasis. In the present study, we examined the effects of orexins on blood glucose levels in response to fasting in normal and streptozotocin-induced diabetic mice. After the injection of orexin-A and orexin-B (0.01-1 nmol/kg, i.v.), the blood glucose levels in both normal mice and diabetic mice in the fasting state decreased. In contrast, neither orexin-A nor orexin-B affected the glucose levels in the animals allowed free access to food. Intracerebroventricular administration of orexin-A and orexin-B was associated with glucose-lowering effects in fasting diabetic mice. The serum insulin level did not significantly change following the administration of orexin-A or orexin-B, in either the normal or the diabetic mice in the fasting state. These results demonstrate that orexins lower the blood glucose levels exclusively in the fasting state. The orexins may stimulate some neural and hormonal network and thereby promote blood glucose utilization.