Dosi Miranda, Scott Laura, Payne Holly, Poldy Jacqueline, Keen John, McGorum Bruce, Malbon Alexandra, Morgan Ruth
Scotland Rural College, Edinburgh, UK.
Royal (Dick) School of Veterinary Studies and Roslin Institute, University of Edinburgh, Roslin, UK.
J Vet Intern Med. 2025 Jul-Aug;39(4):e70143. doi: 10.1111/jvim.70143.
Hyperinsulinaemia (HI) is an important feature of Equine Metabolic Syndrome (EMS). It has been suggested that reduced hepatic clearance of insulin contributes to HI, particularly in humans affected by metabolic dysfunction-associated steatotic liver disease (MASLD).
In obese horses with HI, insulin clearance is impaired and associated with MASLD.
Tissue samples were collected at post-mortem from clinically well-characterized horses with HI (n = 13; basal insulin > 20 mIU/l) and without HI (control; n = 20).
Retrospective observational study. Molecular drivers of hepatic clearance (CAECAM-1, an insulin chaperone protein and IDE-Insulin Degrading Enzyme) were quantified by RT-qPCR and activity, respectively, in liver tissue. Fixed liver sections stained with hematoxylin and eosin (H&E) were assigned a histological score by two blinded observers using an equine liver disease score and a human MASLD score. Triglyceride (TG) content in liver sections, serum liver enzymes, ACTH, basal insulin, and serum triglycerides were also measured.
IDE activity was 2.73 (IQR 4.00 activity/mg of protein) in HI horses and 2.18 (IQR 0.55) in controls (p = 0.07). IDE activity correlated negatively with insulin (rho = 0.561, p = 0.04) but not with liver or serum TG. CEACAM-1 gene expression was higher in the HI group (2.09 ± 1.79 folds) than in controls (0.69 ± 0.62, p = 0.03). Liver disease and MASLD scores were no different between groups, whereas triglyceride liver content was higher in horses with HI (504.83 IQR 217.51 nmol/g) compared to controls (363.58 IQR 67.32 nmol/g, p = 0.04).
MASLD is not consistently present in HI horses, but CAECAM-1 expression is higher.
高胰岛素血症（HI）是马代谢综合征（EMS）的一个重要特征。有人提出，肝脏胰岛素清除率降低会导致高胰岛素血症，特别是在患有代谢功能障碍相关脂肪性肝病（MASLD）的人类中。
在患有高胰岛素血症的肥胖马匹中，胰岛素清除受损并与MASLD相关。
从临床特征明确的患有高胰岛素血症（n = 13；基础胰岛素>20 mIU/l）和无高胰岛素血症（对照组；n = 20）的马匹死后收集组织样本。
回顾性观察研究。分别通过RT-qPCR和活性定量肝组织中肝脏清除的分子驱动因素（CAECAM-1，一种胰岛素伴侣蛋白和IDE-胰岛素降解酶）。两名盲法观察者使用马肝病评分和人类MASLD评分对苏木精和伊红（H&E）染色的固定肝切片进行组织学评分。还测量了肝切片中的甘油三酯（TG）含量、血清肝酶、促肾上腺皮质激素、基础胰岛素和血清甘油三酯。
高胰岛素血症马匹的IDE活性为2.73（IQR 4.00活性/毫克蛋白质），对照组为2.18（IQR 0.55）（p = 0.07）。IDE活性与胰岛素呈负相关（rho = 0.561，p = 0.04），但与肝脏或血清TG无关。HI组的CEACAM-1基因表达（2.09±1.79倍）高于对照组（0.69±0.62，p = 0.03）。两组之间的肝病和MASLD评分无差异，而高胰岛素血症马匹的肝脏甘油三酯含量（504.
