title: Depletion of norepinephrine of the central nervous system Down-regulates the blood glucose level in d-glucose-fed and restraint stress models.
abstract: DSP-4[N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine hydrochloride] is a neurotoxin that depletes norepinephrine. The catecholaminergic system has been implicated in the regulation of blood glucose level. In the present study, the effect of DSP-4 administered intracerebroventricularly (i.c.v.) or intrathecally (i.t.) on blood glucose level was examined in d-glucose-fed and restraint stress mice models. Mice were pretreated once i.c.v. or i.t. with DSP-4 (10-40μg) for 3days, and d-glucose (2g/kg) was fed orally. Blood glucose level was measured 0 (prior to glucose feeding or restraint stress), 30, 60, and 120min after d-glucose feeding or restraint stress. The i.c.v. or i.t. pretreatment with DSP-4 attenuated blood glucose level in the d-glucose-fed model. Plasma corticosterone level was downregulated in the d-glucose-fed model, whereas plasma insulin level increased in the d-glucose-fed group. The i.c.v. or i.t. pretreatment with DSP-4 reversed the downregulation of plasma corticosterone induced by feeding d-glucose. In addition, the d-glucose-induced increase in plasma insulin was attenuated by the DSP-4 pretreatment. Furthermore, i.c.v. or i.t. pretreatment with DSP-4 reduced restraint stress-induced increases in blood glucose levels. Restraint stress increased plasma corticosterone and insulin levels. The i.c.v. pretreatment with DSP-4 attenuated restraint stress-induced plasma corticosterone and insulin levels. Our results suggest that depleting norepinephrine at the supraspinal and spinal levels appears to be responsible for downregulating blood glucose levels in both d-glucose-fed and restraint stress models.
authors.affiliation: Department of Pharmacology, Institute of Natural Medicine, College of Medicine, Hallym University, 39 Hallymdaehak-gil, Chuncheon, Gangwon-do 200-702, Republic of 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, 39 Hallymdaehak-gil, Chuncheon, Gangwon-do 200-702, Republic of 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, 39 Hallymdaehak-gil, Chuncheon, Gangwon-do 200-702, Republic of Korea.
authors.forename: Jae-Ryeong
authors.initials: JR
authors.lastname: Lee
authors.affiliation: Department of Pharmacology, Institute of Natural Medicine, College of Medicine, Hallym University, 39 Hallymdaehak-gil, Chuncheon, Gangwon-do 200-702, Republic of Korea.
authors.forename: Naveen
authors.initials: N
authors.lastname: Sharma
authors.affiliation: 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.
authors.forename: Hong-Won
authors.initials: HW
authors.lastname: Suh
mesh_terms: D000818:Animals; D001596:Benzylamines / Q000008:administration & dosage / Q000633:toxicity; D001786:Blood Glucose / Q000378:metabolism*; D002490:Central Nervous System / Q000187:drug effects / Q000378:metabolism*; D003345:Corticosterone / Q000097:blood; D015536:Down-Regulation; D005947:Glucose / Q000008:administration & dosage*; D007276:Injections, Intraventricular; D007278:Injections, Spinal; D008297:Male; D008813:Mice, Inbred ICR; D009498:Neurotoxins / Q000008:administration & dosage / Q000633:toxicity; D009638:Norepinephrine / Q000378:metabolism*; D012149:Restraint, Physical; D013315:Stress, Psychological / Q000378:metabolism*
chemical_list: D001596:Benzylamines; D001786:Blood Glucose; D009498:Neurotoxins; D005947:Glucose; C012102:DSP 4; D003345:Corticosterone; D009638:Norepinephrine
keywords: Blood glucose; DSP-4; OGTT; Restraint stress; Spinal; Supra spinal