Background and Aim: When glucose homeostasis is disrupted, acute or chronic hyperglycemia may occur. Linalool is a bioactive compound present in several plant species. In the present study, we investigated the effect of linalool on acute hyperglycemia and hypoinsulinemia caused by ketamine-xylazine administration. To clarify the involved mechanism, yohimbine (an α₂-adrenergic receptor antagonist) was used.
Methods: Linalool (2.5, 10, and 40 mg/kg) and yohimbine (0.5 and 2 mg/kg) were injected intraperitoneally (IP) 25 and 20 min before acute hyperglycemia induction, respectively. Acute hyperglycemia was induced with IP administration of a mixture of ketamine (100 mg/kg) and xylazine (10 mg/kg). The tail blood glucose levels were measured. After the last blood glucose level measurement, blood samples were taken to determine serum insulin concentration. To clarify the effects of drugs on blood glucose and serum insulin alterations in conscious animals, IP injections of the high doses of linalool (40 mg/kg) and yohimbine (2 mg/kg) were also performed without ketamine-xylazine treatment. The area under the curves (AUC) and the percentage of blood glucose changes in the period of 30-120 min after ketamine-xylazine injection and the percentage of serum insulin alterations were also calculated.
Results: Blood glucose levels were significantly (p < 0.05) increased at 30, 60, 90, and 120 minutes after ketamine-xylazine injection. In addition, serum insulin concentrations were decreased by ketamine-xylazine administration. Linalool (10 and 40 mg/kg) and yohimbine (2 mg/kg) significantly (p < 0.05) inhibited acute hyperglycemia and hypoinsulinemia. Furthermore, co-administration of ineffective doses of linalool (2.5 mg/kg) and yohimbine (0.5 mg/kg) significantly prevented hyperglycemia and hypoinsulinemia. In conscious animals, no significant differences were observed between groups receiving vehicle and high doses of linalool and yohimbine.
Conclusion: These results showed that linalool could decrease blood glucose levels and increase insulin concentration in the rat model of acute hyperglycemia. Alpha-2 adrenergic receptors might be involved in this effect of linalool.