Zucker Diabetic Fatty (ZDF) Rat Study - Diaphragm vs. Sternohyoid

Type 2 diabetes differs from type 1 diabetes in its pathogenesis. Type 1 diabetic diaphragm has altered gene expression which includes lipid and carbohydrate metabolism, ubiquitination and oxidoreductase activity. The objectives of the present study were to assess respiratory muscle gene expression changes in type 2 diabetes and to determine whether they are greater for the diaphragm than an upper airway muscle. Diaphragm and sternohyoid muscle from Zucker diabetic fatty (ZDF) rats were analyzed with Affymetrix gene expression arrays. The two muscles had 97 and 102 genes, respectively, with at least ±1.5-fold significantly changed expression with diabetes, and these were assigned to gene ontology groups based on over-representation analysis. Several significantly changed groups were common to both muscles, including lipid metabolism, carbohydrate metabolism, muscle contraction, ion transport and collagen, although the number of genes and the specific genes involved differed considerably for the two muscles. In both muscles there was a shift in metabolism gene expression from carbohydrate metabolism toward lipid metabolism, but the shift was greater and involved more genes in diabetic diaphragm than diabetic sternohyoid muscle. Groups present in only diaphragm were blood circulation and oxidoreductase activity. Groups present in only sternohyoid were immune & inflammation and response to stress & wounding, with complement genes being a prominent component. In conclusion, type 2 diabetes-induced gene expression changes in respiratory muscles has both similarities and differences relative to previous data on type 1 diabetes gene expression. Furthermore, the diabetic alterations in gene expression differ between diaphragm and sternohyoid.2型糖尿病的发病机制与1型糖尿病存在显著差异。1型糖尿病患者的膈肌基因表达发生改变，涉及脂质与碳水化合物代谢、泛素化及氧化还原酶活性等生物学过程。本研究旨在评估2型糖尿病状态下呼吸肌的基因表达变化，并明确此类变化在膈肌中是否较上气道肌肉更为显著。研究采用Affymetrix基因表达芯片（Affymetrix gene expression arrays）对扎克糖尿病肥胖（Zucker diabetic fatty, ZDF）大鼠的膈肌与胸骨舌骨肌进行了分析。结果显示，糖尿病状态下，两种肌肉分别有97个和102个基因的表达出现至少±1.5倍的显著变化，随后基于过度代表分析（over-representation analysis）将这些差异基因归入基因本体（Gene Ontology, GO）分组。两种肌肉存在多个共有的显著富集分组，包括脂质代谢、碳水化合物代谢、肌肉收缩、离子转运及胶原相关通路，但二者涉及的基因数量及具体基因存在较大差异。在两种肌肉中，代谢相关基因的表达均呈现从碳水化合物代谢向脂质代谢的转变，但糖尿病膈肌的这种转变程度更为显著，且涉及的基因数量多于糖尿病胸骨舌骨肌。仅在膈肌中富集的分组包括血液循环与氧化还原酶活性相关通路；仅在胸骨舌骨肌中富集的分组则为免疫与炎症、应激与损伤应答，其中补体基因是该类分组的核心组成部分。综上，2型糖尿病诱导的呼吸肌基因表达变化与既往1型糖尿病的相关研究数据既存在相似性，也存在明显差异。此外，糖尿病所致的基因表达改变在膈肌与胸骨舌骨肌之间也存在显著不同。