The modulatory roles of oxyntomodulin and glucagon-like peptide 1 administered spinally in the regulation of the blood glucose level

Abstract

Oxyntomodulin is known as a regulator of the blood glucose homeostasis and food intake. In the present study, the possible roles of oxyntomodulin receptor (GCGR/GLP-1) located in the spinal cord for the regulation of the blood glucose level was investigated in ICR mice. We found in the present study that intrathecal (i.t.) injection with oxyntomodulin (from 1 to 10 μg) or glucagon-like peptide-1 (GLP-1; from 1 to 10 μg) alone did not affect the blood glucose level. However, i.t. administration with oxyntomodulin, but not GLP-1, caused a reduction of the blood glucose level in D-glucose-fed model. The oxyntomodulininduced reduction of the blood glucose level in D-glucose-fed model is followed by reduction of insulin level. Furthermore, the i.t. co-administration of oxyntomodulin with GLP-1 caused a profound up-regulation of the blood glucose level. The profound hyperglycemic effect shown by co-treatment with oxyntomodulin and GLP-1 caused a profound up-regulation of plasma insulin level. Our results suggest that the activation of oxyntomodulin system present in the spinal cord may play significant modulatory roles in the reduction of the blood glucose level in D-glucose-fed model. Furthermore, GLP-1 located in the spinal cord shows a synergistic interaction with oxyntomodulin for producing hyperglycemia.