Ghrelin administered spinally increases the blood glucose level in mice

• I.t. with ghrelin caused an elevation of the blood glucose level.
• I.t. pretreatment with YIL781 attenuated ghrelin-induced hyperglycemic effect.
• Enhanced insulin level by ghrelin was reduced by i.t. pretreatment with YIL781.
• I.t. pretreatment with GLP-1 did not affect ghrelin-induced hyperglycemia.
• I.t. with ghrelin increased blood glucose level in d-glucose-fed model.

Ghrelin is known as a regulator of the blood glucose homeostasis and food intake. In the present study, the possible roles of ghrelin located in the spinal cord in the regulation of the blood glucose level were investigated in ICR mice. We found that intrathecal (i.t.) injection with ghrelin (from 1 to 10 μg) caused an elevation of the blood glucose level. In addition, i.t. pretreatment with YIL781 (ghrelin receptor antagonist; from 0.1 to 5 μg) markedly attenuated ghrelin-induced hyperglycemic effect. The plasma insulin level was increased by ghrelin. The enhanced plasma insulin level by ghrelin was reduced by i.t. pretreatment with YIL781. However, i.t. pretreatment with glucagon-like peptide-1 (GLP-1; 5 μg) did not affect the ghrelin-induced hyperglycemia. Furthermore, i.t. administration with ghrelin also elevated the blood glucose level, but in an additive manner, in d-glucose-fed model. Our results suggest that the activation of ghrelin receptors located in the spinal cord plays important roles for the elevation of the blood glucose level.