title: Repaglinide, but not nateglinide administered supraspinally and spinally exerts an anti-diabetic action in d-glucose fed and streptozotocin-treated mouse models.
abstract: We have recently demonstrated that some anti-diabetic drugs such as biguanide and thizolidinediones administered centrally modulate the blood glucose level, suggesting that orally administered anti-diabetic drugs may modulate the blood glucose level by acting on central nervous system. The present study was designed to explore the possible action of another class of anti-diabetic drugs, glinidies, administered centrally on the blood glucose level in ICR mice. Mice were administered intracerebroventricularly (i.c.v.) or intrathecally (i.t.) with 5 to 30 µg of repaglinide or nateglinide in D-glucose-fed and streptozotocin (STZ)-treated models. We found that i.c.v. or i.t. injection with repaglinide dose-dependently attenuated the blood glucose level in D-glucose-fed model, whereas i.c.v. or i.t. injection with nateglinide showed no modulatory action on the blood glucose level in D-glucose-fed model. Furthermore, the effect of repaglinide administered i.c.v. or i.t. on the blood glucose level in STZ-treated model was studied. We found that repaglinide administered i.c.v. slightly enhanced the blood glucose level in STZ-treated model. On the other hand, i.t. injection with repaglinide attenuated the blood glucose level in STZ-treated model. The plasma insulin level was enhanced by repaglinide in D-glucose-fed model, but repaglinide did not affect the plasma insulin level in STZ-treated model. In addition, nateglinide did not alter the plasma insulin level in both D-glucose-fed and STZ-treated models. These results suggest that the anti-diabetic action of repaglinide appears to be, at least, mediated via the brain and the spinal cord as revealed in both D-glucose fed and STZ-treated models.
authors.affiliation: Department of Pharmacology, Institute of Natural Medicine, College of Medicine, Hallym University, Chuncheon 200-702, Korea.
authors.forename: Yun-Beom
authors.initials: YB
authors.lastname: Sim
authors.affiliation: Department of Pharmacology, Institute of Natural Medicine, College of Medicine, Hallym University, Chuncheon 200-702, Korea.
authors.forename: Soo-Hyun
authors.initials: SH
authors.lastname: Park
authors.affiliation: Department of Pharmacology, Institute of Natural Medicine, College of Medicine, Hallym University, Chuncheon 200-702, Korea.
authors.forename: Yu-Jung
authors.initials: YJ
authors.lastname: Kang
authors.affiliation: Department of Pharmacology, Institute of Natural Medicine, College of Medicine, Hallym University, Chuncheon 200-702, Korea.
authors.forename: Sung-Su
authors.initials: SS
authors.lastname: Kim
authors.affiliation: Department of Pharmacology, Institute of Natural Medicine, College of Medicine, Hallym University, Chuncheon 200-702, Korea.
authors.forename: Chea-Ha
authors.initials: CH
authors.lastname: Kim
authors.affiliation: Department of Pharmacology, Institute of Natural Medicine, College of Medicine, Hallym University, Chuncheon 200-702, Korea.
authors.forename: Su-Jin
authors.initials: SJ
authors.lastname: Kim
authors.affiliation: Department of Pharmacology, Institute of Natural Medicine, College of Medicine, Hallym University, Chuncheon 200-702, Korea.
authors.forename: Su-Min
authors.initials: SM
authors.lastname: Lim
authors.affiliation: Department of Pharmacology, Institute of Natural Medicine, College of Medicine, Hallym University, Chuncheon 200-702, Korea.
authors.forename: Jun-Sub
authors.initials: JS
authors.lastname: Jung
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, Hallym University, Chuncheon 200-702, Korea.
authors.forename: Ohk-Hyun
authors.initials: OH
authors.lastname: Ryu
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, Hallym University, Chuncheon 200-702, Korea.
authors.forename: Moon-Gi
authors.initials: MG
authors.lastname: Choi
authors.affiliation: Department of Pharmacology, Institute of Natural Medicine, College of Medicine, Hallym University, Chuncheon 200-702, Korea.
authors.forename: Hong-Won
authors.initials: HW
authors.lastname: Suh
keywords: Blood glucose; Glinides; Spinal; Streptozotocin; Supraspinal