Effects of dexmedetomidine on insulin secretion from rat pancreatic β cells.
OBJECTIVE
Dexmedetomidine 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.


METHODS
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 µM) was added to the chamber.


RESULTS
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 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.


CONCLUSIONS
Dexmedetomidine had no effect on insulin secretion at sedative dose, whereas it significantly inhibited insulin secretion at supraclinical high concentrations mainly via the α2-adrenoceptor.
Department of Anesthesiology and Intensive Care Medicine, Kochi Medical School, Kohasu, Oko-cho, Nankoku, Kochi, 783-8505, Japan.
Tetsuya
T
Takahashi
Department of Anesthesiology and Intensive Care Medicine, Kochi Medical School, Kohasu, Oko-cho, Nankoku, Kochi, 783-8505, Japan. takashika@kochi-u.ac.jp.
Takashi
T
Kawano
Department of Dental Anesthesiology, Tokushima University School of Dentistry, Tokushima, Japan.
Satoru
S
Eguchi
Department of Anesthesiology and Intensive Care Medicine, Kochi Medical School, Kohasu, Oko-cho, Nankoku, Kochi, 783-8505, Japan.
Haidong
H
Chi
Department of Anesthesiology and Intensive Care Medicine, Kochi Medical School, Kohasu, Oko-cho, Nankoku, Kochi, 783-8505, Japan.
Hideki
H
Iwata
Department of Anesthesiology and Intensive Care Medicine, Kochi Medical School, Kohasu, Oko-cho, Nankoku, Kochi, 783-8505, Japan.
Masataka
M
Yokoyama
D000818:Animals; D020927:Dexmedetomidine / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism; D006993:Hypnotics and Sedatives / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015016:Yohimbine / Q000494:pharmacology
D006993:Hypnotics and Sedatives; D007328:Insulin; D015016:Yohimbine; D020927:Dexmedetomidine; D005947:Glucose