The effects of an alpha-2-adrenoceptor agonist, antagonist, and their combination on the blood insulin, glucose, and glucagon concentrations in insulin sensitive and dysregulated horses

J.R Box,N.P Karikoski,H.E Tanskanen,M.R Raekallio

doi:10.1016/j.tvjl.2021.105610

J.R Box, N.P Karikoski + Show 2 more

Open Access

https://doi.org/10.1016/j.tvjl.2021.105610

Copy DOI

Abstract

Alpha-2-adrenoceptor agonists are sedatives that can cause fluctuations in serum insulin and blood glucose (BG) concentrations in horses. The objectives of this study were to investigate the effects of detomidine and vatinoxan on BG, insulin, and glucagon concentrations in horses with and without insulin dysregulation (ID). In a blinded cross-over design, eight horses with ID and eight horses without ID were assigned to each of four treatments: detomidine (0.02 mg/kg; DET), vatinoxan (0.2 mg/kg; VAT), detomidine + vatinoxan (DET + VAT), and saline control (SAL). Blood samples were taken at 0, 1, 2, 4, 6, and 8 h. Change from baseline was used as the response in modelling, and the differences between treatments were evaluated with repeated measures analysis of covariance. P values ≤0.05 were considered significant.Comparing DET vs. SAL and DET vs. DET + VAT, insulin was higher at 2 h in the non-ID group and 2 and 4 h in the ID group. There was no difference in insulin between SAL and DET + VAT or VAT. Comparing DET vs. SAL, BG was higher at 1 and 2 h then was lower at 4 h in both ID and non-ID groups. At 1 h in both groups, BG after DET + VAT was lower than after DET but higher than after SAL. Comparing DET vs. SAL, glucagon was lower at 1 h in the ID group and 1 and 2 h in the non-ID group. Vatinoxan was effective in preventing detomidine-induced hyperglycaemia as well as the subsequent insulin increase in horses with ID.

Highlights

An increase in plasma glucose concentration is induced by all α2-adrenoceptor agonists commonly used for sedation in horses, i.e. xylazine (Ringer et al, 2013; Kullmann et al, 2014; Kritchevsky et al, 2020), detomidine (Kullmann et al, 2014; Tapio et al, 2018; Kritchevsky et al, 2020), romifidine (Ringer et al, 2013; Kullmann et al, 2014; Pakkanen et al, 2018) and medetomidine (Grimsrud et al, 2012; Tapio et al, 2019)
One study could not verify the effects of vatinoxan on plasma insulin concentration in horses, likely due to most of the results being below the quantification limit of the assay used (Pakkanen et al, 2018)
The objectives of this study were to investigate the effects of an α2-adrenoceptor agonist and peripherally acting antagonist on plasma glucose, insulin, and glucagon concentrations in horses with normal and reduced insulin sensitivity

Summary

Introduction

An increase in plasma glucose concentration is induced by all α2-adrenoceptor agonists commonly used for sedation in horses, i.e. xylazine (Ringer et al, 2013; Kullmann et al, 2014; Kritchevsky et al, 2020), detomidine (Kullmann et al, 2014; Tapio et al, 2018; Kritchevsky et al, 2020), romifidine (Ringer et al, 2013; Kullmann et al, 2014; Pakkanen et al, 2018) and medetomidine (Grimsrud et al, 2012; Tapio et al, 2019). The centrally mediated sedative effects of α2adrenoceptor agonists are not markedly affected (Vainionpää et al, 2013; De Vries et al, 2016; Tapio et al, 2018, 2019), but peripheral vasoconstriction and concomitant cardiovascular changes are alleviated. This has been demonstrated in many species including horses (De Vries et al, 2016; Tapio et al, 2018, 2019). One study could not verify the effects of vatinoxan on plasma insulin concentration in horses, likely due to most of the results being below the quantification limit of the assay used (Pakkanen et al, 2018)

Objectives

Methods

Results

Conclusion