Herndon A M, Breshears M A, McFarlane D
Department of Physiological Sciences, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, OK 74078, USA.
Department of Veterinary Pathobiology, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, OK 74078, USA.
J Comp Pathol. 2014 Nov;151(4):352-62. doi: 10.1016/j.jcpa.2014.06.004. Epub 2014 Aug 11.
The pathogenesis of β-cell dysfunction leading to pancreatic β-cell failure seen in type 2 diabetes mellitus is incompletely understood. Pancreatic tissues were collected from nine control cats and nine diabetic cats and labelled immunohistochemically to examine expression of interleukin (IL)-1β, insulin, islet amyloid polypeptide (IAPP) and 4-hydroxynonenal (4-HNE). Thioflavin-S was used to stain for amyloid. All control cats showed positive labelling for IL-1β and 4-HNE. Diabetic cats showed varying degrees of inflammation and oxidative modification, owing in large part to the very small amount of islet structure remaining in the typical diabetic cat pancreas. Amyloid deposition was identified in 8/9 diabetic cats and 1/9 control cats. In order to validate these findings, paired biopsy samples taken from an additional group of cats enrolled in a study of obesity and hyperglycaemia (sampling at baseline and after 8-16 weeks of obesity and hyperglycaemia) were labelled for IL-1β and 4-HNE. A similar pattern of labelling was identified in the baseline samples to that seen in control cats. A significant increase in IL-1β and 4-HNE expression was seen after a period of hyperglycaemia and obesity. Taken together, these findings suggest that while present in normal cats, markers of inflammation and oxidative modification increase very early during the development of disease. Future studies focusing on these earlier time points are needed to understand the factors that function in protection of the islet β cell and the development of islet pathology in type 2 diabetes mellitus in the cat.
2型糖尿病中导致胰腺β细胞功能障碍并最终致使胰腺β细胞衰竭的发病机制尚未完全明确。从9只对照猫和9只糖尿病猫身上采集胰腺组织，进行免疫组织化学标记，以检测白细胞介素（IL）-1β、胰岛素、胰岛淀粉样多肽（IAPP）和4-羟基壬烯醛（4-HNE）的表达。使用硫黄素-S对淀粉样物质进行染色。所有对照猫的IL-1β和4-HNE标记均呈阳性。糖尿病猫表现出不同程度的炎症和氧化修饰，这在很大程度上归因于典型糖尿病猫胰腺中残留的胰岛结构非常少。在9只糖尿病猫中有8只发现淀粉样物质沉积，而在9只对照猫中有1只发现淀粉样物质沉积。为了验证这些发现，对另一组参与肥胖和高血糖研究的猫（在肥胖和高血糖8 - 16周的基线期和之后进行采样）采集的配对活检样本进行IL-1β和4-HNE标记。在基线样本中发现了与对照猫相似的标记模式。在经历一段时间的高血糖和肥胖后，IL-1β和4-HNE的表达显著增加。综上所述，这些发现表明，虽然炎症和氧化修饰标记物在正常猫中也存在，但在疾病发展过程中很早就会增加。需要针对这些更早时间点开展进一步研究，以了解在猫的2型糖尿病中对胰岛β细胞起保护作用的因素以及胰岛病理的发展情况。
