Meglitinides (
nateglinide and
repaglinide) are widely used oral drugs for the treatment of type II
diabetes mellitus. In the present study, the effects of meglinitides administered supraspinally on
kainic acid (KA)-induced hippocampal neuronal cell death and
hyperglycemia were studied in ICR mice. Mice were pretreated intracerebroventricularly (i.c.v.) with 30 μg of
nateglinide and
repaglinide for 10 min and then, mice were administered i.c.v. with KA (0.1 μg). The neuronal cell death in the CA3 region in the hippocampus was assessed 24h after KA administration and the
blood glucose level was measured 30, 60, and 120 min after KA administration. We found that i.c.v. pretreatment with
repaglinide attenuated the KA-induced neuronal cell death in CA3 region of the hippocampus and
hyperglycemia. However,
nateglinide pretreated i.c.v. did not affect the KA-induced neuronal cell death and
hyperglycemia. In addition, KA administered i.c.v. caused an elevation of plasma
corticosterone level and a reduction of the plasma
insulin level. Furthermore, i.c.v. pretreatment with
repaglinide attenuated KA-induced up-regulation of plasma
corticosterone level. Furthermore, i.c.v. administration of
repaglinide alone increased plasma
insulin level and
repaglinide pretreated i.c.v. caused a reversal of KA-induced hypoinsulinemic effect. Our results suggest that supraspinally administered
repaglinide, but not
nateglinide, exerts a protective effect against the KA-induced neuronal cells death in CA3 region of the hippocampus. The
neuroprotective effect of
repaglinide appears to be mediated by lowering the
blood glucose level induced by KA.