Effects of dexmedetomidine on insulin secretion from rat pancreatic β cells
Effects of dexmedetomidine on insulin secretion from rat pancreatic β cells
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DOI：
10.1007/s00540-014-1943-2
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发表时间：
2015-06-01
影响因子：
2.8
通讯作者：
Yokoyama, Masataka
中科院分区：
文献类型：
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作者：
Takahashi, Tetsuya;Kawano, Takashi;Yokoyama, Masataka
右美托咪定是一种选择性α(2)-肾上腺素能受体激动剂和咪唑啉受体激动剂，这两种受体激动剂都能影响胰岛素的分泌。在此，我们研究了临床相关浓度的右美托咪定在体内条件下对胰岛素分泌的影响。为了进行体内口服葡萄糖耐量试验，将雄性SD大鼠随机分为三组(每组7只)：低剂量组(L组)和高剂量组(H组)和对照组(C组)。在体外灌流研究中，胰岛素从分离的胰岛中释放出来是在血糖逐步变化的过程中测量的。在OGTT试验中，H组在糖负荷后30、60、90min的胰岛素水平明显低于C组。L组胰岛素水平在各时间点均与C组相当。在灌流研究中，右旋美托咪定以浓度依赖的方式抑制葡萄糖刺激的胰岛素分泌。当与α(2)-肾上腺素能受体阻滞剂育亨宾联合治疗时，右美托咪定不利地增加了葡萄糖诱导的胰岛素分泌。然而，与α(2)-肾上腺素能和咪唑啉受体拮抗剂咪唑克生联合应用，可完全阻断右美托咪啶的作用。在镇静剂量下，右美托咪定对胰岛素的分泌没有影响，而在临床上高浓度时，它主要通过α(2)-肾上腺素能受体显著抑制胰岛素的分泌。
Dexmedetomidine acts as a selective alpha(2)-adrenergic receptor agonist and an imidazoline receptor agonist, both of which are known to affect insulin secretion. Here, we investigated the effects of clinically relevant concentrations of dexmedetomidine on insulin secretion under in vivo conditions. Furthermore, its underlying mechanisms were examined using isolated islets in vitro.For the in vivo oral glucose tolerance test (OGTT), male Sprague-Dawley rats were randomly allocated to one of three groups (n = 7 in each group): two groups infused with dexmedetomidine at a low (group L) or a high (group H) dose, and one control group infused with the same amount of saline (group C). For the in vitro perifusion study, insulin released from isolated islets was measured during stepwise changes in glucose. Dexmedetomidine (0.1-100 A mu M) was added to the chamber.During the OGTT test, the insulin levels in group H were significantly lower than those in group C at 30, 60, and 90 min after glucose load. On the other hand, insulin levels in group L were comparable to those of group C at all time points. In the perfusion study, dexmedetomidine inhibited glucose-stimulated insulin secretion in a concentration-dependent manner. When co-treated with yohimbine, an alpha(2)-adrenoceptor blocker, dexmedetomidine adversely increased glucose-induced insulin secretion. However, co-treatment with idazoxan, an antagonist for alpha(2)-adrenergic and imidazoline receptors, completely abolished the action of dexmedetomidine.Dexmedetomidine had no effect on insulin secretion at sedative dose, whereas it significantly inhibited insulin secretion at supraclinical high concentrations mainly via the alpha(2)-adrenoceptor.