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KMID : 0043320150380050921
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Archives of Pharmacal Research
2015 Volume.38 No. 5 p.921 ~ p.929
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Involvement of α2-adrenergic receptor in the regulation of the blood glucose level induced by immobilization stress
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Kang Yu-Jung
Sim Yun-Beom
Park Soo-Hyun
Sharma Naveen
Suh Hong-Won
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Abstract
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The blood glucose profiles were characterized after mice were forced into immobilization stress with various exposure durations. The blood glucose level was significantly enhanced by immobilization stress for 30 min or 1 h, respectively. On the other hand, the blood glucose level was not affected in the groups which were forced into immobilization stress for 2 or 4 h. We further examined the effect of yohimbine (an α2-adrenergic receptor antagonist) administered systemically or centrally in the immobilization stress model. Mice were pretreated intraperitoneally (i.p.; from 0.5 to 5 mg/kg), intracerebroventricularly (i.c.v.; from 1 to 10 μg/5 μl), or intrathecally (i.t.; from 1 to 10 μg/5 μl) with yohimbine for 10 min and then, forced into immobilization stress for 30 min. The blood glucose level was measured right after immobilization stress. We found that up-regulation of the blood glucose level induced by immobilization stress was abolished by i.p. pretreatment with yohimbine. And the immobilization stress-induced blood glucose level was not inhibited by i.c.v. or i.t. pretreatment with yohimbine at a lower dose (1 μg/5 μl). However, immobilization stress-induced blood glucose level was significantly inhibited by i.c.v. or i.t. pretreatment with yohimbine at higher doses (5 and 10 μg/5 μl). In addition, the i.p. (5 mg/kg), i.c.v. (10 μg/5 μl), or i.t. (10 μg/5 μl) pretreatment with yohimbine reduced hypothalamic glucose transporter 4 expression. The involvement of α2-adrenergic receptor in regulation of immobilization stress- induced blood glucose level was further confirmed by the i.p, i.c.v, or i.t pretreatment with idazoxan, another specific α2-adrenergic receptor antagonist. Finally, i.p., i.c.v., or i.t. pretreatment with yohimbine attenuated the blood glucose level in d-glucose-fed model. We suggest that α2-adrenergic receptors located at the peripheral, the brain and the spinal cord play important roles in the up-regulation of the blood glucose level in immobilization stress.
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KEYWORD
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Immobilization stress, Yohimbine, Spinal cord, Blood glucose, Central, Systemic
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