Effects of nateglinide and repaglinide administered intracerebroventricularly on the CA3 hippocampal neuronal cell death and hyperglycemia induced by kainic acid in mice.
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.
Department of Pharmacology, Institute of Natural Medicine, College of Medicine, Hallym University, 39 Hallymdaehak-gil, Chuncheon, Gangwon-do 200-702, Republic of Korea.
Chea-Ha
CH
Kim
Department of Pharmacology, Institute of Natural Medicine, College of Medicine, Hallym University, 39 Hallymdaehak-gil, Chuncheon, Gangwon-do 200-702, Republic of Korea.
Soo-Hyun
SH
Park
Department of Pharmacology, Institute of Natural Medicine, College of Medicine, Hallym University, 39 Hallymdaehak-gil, Chuncheon, Gangwon-do 200-702, Republic of Korea.
Yun-Beom
YB
Sim
Department of Pharmacology, Institute of Natural Medicine, College of Medicine, Hallym University, 39 Hallymdaehak-gil, Chuncheon, Gangwon-do 200-702, Republic of Korea.
Sung-Su
SS
Kim
Department of Pharmacology, Institute of Natural Medicine, College of Medicine, Hallym University, 39 Hallymdaehak-gil, Chuncheon, Gangwon-do 200-702, Republic of Korea.
Su-Jin
SJ
Kim
Department of Pharmacology, Institute of Natural Medicine, College of Medicine, Hallym University, 39 Hallymdaehak-gil, Chuncheon, Gangwon-do 200-702, Republic of Korea.
Su-Min
SM
Lim
Department of Pharmacology, Institute of Natural Medicine, College of Medicine, Hallym University, 39 Hallymdaehak-gil, Chuncheon, Gangwon-do 200-702, Republic of Korea.
Jun-Sub
JS
Jung
Department of Pharmacology, Institute of Natural Medicine, College of Medicine, Hallym University, 39 Hallymdaehak-gil, Chuncheon, Gangwon-do 200-702, Republic of Korea. Electronic address: hwsuh@hallym.ac.kr.
Hong-Won
HW
Suh
D000818:Animals; D001786:Blood Glucose / Q000187:drug effects* / Q000378:metabolism; D056654:CA3 Region, Hippocampal / Q000187:drug effects*; D002219:Carbamates / Q000008:administration & dosage / Q000494:pharmacology*; D016923:Cell Death; D003345:Corticosterone / Q000097:blood; D003510:Cyclohexanes / Q000008:administration & dosage / Q000494:pharmacology*; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D057967:Infusions, Intraventricular; D007328:Insulin / Q000097:blood; D007608:Kainic Acid / Q000633:toxicity; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D000077715:Nateglinide; D009474:Neurons / Q000187:drug effects*; D010649:Phenylalanine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D010880:Piperidines / Q000008:administration & dosage / Q000494:pharmacology*
D001786:Blood Glucose; D002219:Carbamates; D003510:Cyclohexanes; D018690:Excitatory Amino Acid Agonists; D007004:Hypoglycemic Agents; D007328:Insulin; D010880:Piperidines; D000077715:Nateglinide; D010649:Phenylalanine; C072379:repaglinide; D007608:Kainic Acid; D003345:Corticosterone
Blood glucose; Kainic acid; Megltinide; Neuronal cell death