Effects of alpha-2-adrenoceptor agonism and antagonism on equine blood insulin and glucose concentrations after oral carbohydrate load

Alpha-2-adrenoceptor agonist detomidine is a commonly used sedative agent in horses. In addition to the sedative effect, detomidine has been reported to elicit changes in energy metabolism such as hypoinsulinaemia and hyperglycaemia. This study aimed to investigate the effects of detomidine with and without peripherally acting alpha-2-adrenoceptor antagonist vatinoxan on insulin and blood glucose (BG) concentrations in horses after a standard dose of oral carbohydrates. Sixteen horses were assigned to four intravenous treatments in a randomized cross-over design: saline (SAL), detomidine (0.02 mg/kg; DET), vatinoxan (0.2 mg/kg; VAT), and a combination of detomidine and vatinoxan (DET+VAT). Horses were administered corn syrup (0.45 mL/kg) immediately before each treatment. Blood samples were collected until 360 min. The differences between treatments were evaluated with repeated measures analysis of covariance and change from baseline was used as a response. P<0.05 was considered significant. After oral carbohydrate load, DET reduced insulin (median 30 min nadir 3.7, min–max 0.6–7.4 µIU/mL) significantly compared with SAL (P<0.0001; 17.4, 9.3–65.4 µIU/mL) and DET+VAT (P=0.0005; 6.4, 2.9–12.9 µIU/mL). BG increased significantly after DET (peak; 13.5, 8.8–15.8 mmol/L) compared with SAL (P<0.0001; 8.7, 6.9–12.4 mmol/L) and DET+VAT (P<0.0001; 8.5, 6.8–10.6 mmol/L). Vatinoxan alone reduced BG (peak median 7.6, 7.0–9.9 mmol/L) compared with SAL (P=0.02) and delayed insulin responses to carbohydrates. In conclusion, vatinoxan alleviated the detomidine-induced changes (DET+VAT compared to DET) in insulin and BG after oral carbohydrate load. Additionally, vatinoxan is potentially able to modulate BG concentration and insulin response after oral carbohydrate administration in horses, but more research is warranted.