Galinelli Nicolas C, Bamford Nicholas J, Erdody Madison L, Warnken Tobias, de Laat Melody A, Sillence Martin N, Harris Patricia A, Bailey Simon R
Melbourne Veterinary School, The University of Melbourne, Parkville, Victoria, Australia.
Boehringer Ingelheim Vetmedica GmbH, Ingelheim am Rhein, Germany.
Domest Anim Endocrinol. 2025 Jan;90:106893. doi: 10.1016/j.domaniend.2024.106893. Epub 2024 Oct 20.
The role of dopamine in the regulation of insulin secretion in horses is poorly understood and requires further investigation. Pituitary pars intermedia dysfunction (PPID) is associated with decreased activity of dopaminergic neurons which normally suppress peptide hormone secretion from the pituitary pars intermedia. A high proportion of horses with PPID also have insulin dysregulation (ID), characterised by post-prandial hyperinsulinaemia and/or tissue insulin resistance, which are risk factors for the development of laminitis. The aim of this study was to investigate the effects of alpha-methyl-para-tyrosine (AMPT), a tyrosine hydroxylase inhibitor that reduces dopamine production, on insulin sensitivity and the post-prandial insulin response to a glucose-containing meal. Six healthy Standardbred horses were enrolled in a placebo-controlled randomised crossover study, in which one dose of AMPT (40 mg/kg BW) or placebo was administered orally, prior to performing an in-feed oral glucose test (OGT) and a frequently sampled intravenous glucose tolerance test (FSIGTT). Dopamine reduction by AMPT was confirmed by an increase in plasma prolactin concentration and the lack of post-prandial increase in plasma dopamine concentration compared to placebo. Post-prandial insulin responses, both peak and AUCi, were increased after AMPT compared to placebo (P=0.048 and P=0.005, respectively), without affecting blood glucose concentrations. However, one dose of AMPT did not appear to affect tissue sensitivity as assessed by the FSIGTT. This study confirmed that dopamine plays a role in the regulation of insulin secretion in horses, as it does in other species, whereby the post-prandial release of dopamine into the circulation may inhibit pancreatic insulin secretion. Further studies are required to evaluate different dosing protocols for AMPT, and to further investigate the links between PPID, ID and laminitis risk in horses.
多巴胺在调节马胰岛素分泌中的作用尚不清楚，需要进一步研究。垂体中间叶功能障碍（PPID）与多巴胺能神经元活性降低有关，这些神经元通常抑制垂体中间叶肽类激素的分泌。高比例的患有PPID的马也存在胰岛素调节异常（ID），其特征为餐后高胰岛素血症和/或组织胰岛素抵抗，这些都是发生蹄叶炎的危险因素。本研究的目的是调查α-甲基-对-酪氨酸（AMPT），一种降低多巴胺生成的酪氨酸羟化酶抑制剂，对胰岛素敏感性以及对含葡萄糖餐食的餐后胰岛素反应的影响。六匹健康的标准赛马参加了一项安慰剂对照的随机交叉研究，在进行饲料口服葡萄糖试验（OGT）和频繁采样静脉葡萄糖耐量试验（FSIGTT）之前，口服一剂AMPT（40mg/kg体重）或安慰剂。与安慰剂相比，血浆催乳素浓度升高以及餐后血浆多巴胺浓度没有增加，证实了AMPT降低了多巴胺。与安慰剂相比，AMPT给药后餐后胰岛素反应的峰值和AUCi均增加（分别为P=0.048和P=0.005），而不影响血糖浓度。然而，一剂AMPT似乎并未影响FSIGTT评估的组织敏感性。本研究证实，多巴胺在马胰岛素分泌调节中发挥作用，就像在其他物种中一样，即多巴胺餐后释放到循环中可能抑制胰腺胰岛素分泌。需要进一步研究来评估AMPT的不同给药方案，并进一步研究马中PPID、ID和蹄叶炎风险之间的联系。
