title: Activation of spinal α2 adrenergic receptors induces hyperglycemia in mouse though activating sympathetic outflow.
abstract: The roles of α2-adrenergic receptors located in the spinal cord in the regulation of blood glucose levels were studied in imprinting control region (ICR) mice. Mice were treated intrathecally (i.t.) with clonidine or yohimbine, and the blood glucose levels were measured at 0, 30, 60 and 120min after i.t. administration. The i.t. injection with clonidine caused a pronounced elevation of the blood glucose levels in a dose-dependent manner. Clonidine-induced hyperglycemic effect was dose-dependently attenuated by i.t. pretreatment with yohimbine. Furthermore, plasma insulin level was attenuated by clonidine, and yohimbine pretreatment reversed partially, but significantly, clonidine-induced down-regulation of the plasma insulin level. I.t. pretreatment with pertussis toxin (PTX) almost abolished the hyperglycemic effect induced by clonidine. PTX pretreatment reversed the induced down-regulation of the insulin level. In addition, i.t. pretreatment with N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) or intraperitoneal (i.p.) pretreatment with mifepristone, hexamethonium and 6-hydroxydopamine (6-OHDA) attenuated the hyperglycemic effect induced by clonidine. I.t. injected clonidine significantly increased plasma corticosterone level. The elevated blood glucose level induced by clonidine was significantly decreased in adrenalectomized (ADX) mice. Our results suggest that the α2-adrenergic receptors located in the spinal cord play important roles for the elevation of the blood glucose level. The hyperglycemic effect induced by clonidine appears to be mediated by a reduction of the plasma insulin level. In addition, glucocortioid system appears to be involved in clonidine-induced hyperglycemic effect. Furthermore, the clonidine-induced hyperglycemia appears to be mediated via activating the spinal nerves or peripheral sympathetic nervous system.
authors.affiliation: Department of Pharmacology, Institute of Natural Medicine, College of Medicine Hallym University, 39 Hallymdaehak-gil, Gangwon-do, Chuncheon 200-702, Republic of 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, 39 Hallymdaehak-gil, Gangwon-do, Chuncheon 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, Gangwon-do, Chuncheon 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, Gangwon-do, Chuncheon 200-702, Republic of 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, 39 Hallymdaehak-gil, Gangwon-do, Chuncheon 200-702, Republic of Korea.
authors.forename: Jun-Sub
authors.initials: JS
authors.lastname: Jung
authors.affiliation: Department of Pharmacology, Institute of Natural Medicine, College of Medicine Hallym University, 39 Hallymdaehak-gil, Gangwon-do, Chuncheon 200-702, Republic of Korea. Electronic address: hwsuh@hallym.ac.kr.
authors.forename: Hong-Won
authors.initials: HW
authors.lastname: Suh
mesh_terms: D000320:Adrenergic Fibers / Q000187:drug effects / Q000378:metabolism*; D058647:Adrenergic alpha-2 Receptor Agonists / Q000008:administration & dosage*; D058669:Adrenergic alpha-2 Receptor Antagonists / Q000008:administration & dosage*; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D003000:Clonidine / Q000008:administration & dosage; D006943:Hyperglycemia / Q000139:chemically induced / Q000378:metabolism*; D007278:Injections, Spinal; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism*; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism*; D015016:Yohimbine / Q000008:administration & dosage
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D001786:Blood Glucose; D018341:Receptors, Adrenergic, alpha-2; D015016:Yohimbine; D003000:Clonidine
keywords: Adrenalectomy; Adrenergic receptors; Blood glucose; Glucocorticoid; Pertussis toxin; Spinal cord