• Tetsuya Takahashi, Takashi Kawano, Satoru Eguchi, Haidong Chi, Hideki Iwata, and Masataka Yokoyama.
• Department of Anesthesiology and Intensive Care Medicine, Kochi Medical School, Kohasu, Oko-cho, Nankoku, Kochi, 783-8505, Japan.
• J Anesth. 2015 Jun 1; 29 (3): 396-402.

PurposeDexmedetomidine acts as a selective α2-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.MethodsFor 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 µM) was added to the chamber.ResultsDuring 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 α2-adrenoceptor blocker, dexmedetomidine adversely increased glucose-induced insulin secretion. However, co-treatment with idazoxan, an antagonist for α2-adrenergic and imidazoline receptors, completely abolished the action of dexmedetomidine.ConclusionsDexmedetomidine had no effect on insulin secretion at sedative dose, whereas it significantly inhibited insulin secretion at supraclinical high concentrations mainly via the α2-adrenoceptor.

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