Supplementary Material for: Diabetic Phenotype in the Small Intestine of Zucker Diabetic Fatty Rats

<b><i>Background/Aims:</i></b> In contrast to streptozotocin (STZ)-induced rodent models of diabetes, there are no thorough characterizations of the intestinal phenotype and the underlying changes in the global gene-expression of genetic models of diabetes, such as the Zucker diabetic fatty (ZDF) rat. The aim of the present study was to characterize the intestine in the ZDF rat. <b><i>Methods:</i></b> The intestine of ZDF rats and lean controls was examined macroscopically and histologically, and ribonucleic acid sequencing (RNAseq) was performed in samples of jejunal mucosa. <b><i>Results:</i></b> We observed an increased mass and length of the small and large intestines in ZDF rats. RNAseq showed an increased expression of <i>Pdk2</i> and <i>Pdk4</i>, which are involved in the regulation of glucose and fatty acid metabolism, and increased expression of genes involved in gluconeogenesis and peroxisomal beta-oxidation in jejunal mucosa. <b><i>Conclusion:</i></b> Intestinal enlargement in ZDF rats is likely driven by increased food intake, since (i) it also occurs in obese and normoglycemic Zucker fatty rats, and (ii) insulin treatment of STZ-induced diabetic rats reduced the food intake and mass of the small intestine. Results from RNAseq indicate that small intestinal epithelial cells in ZDF rats have developed insulin resistance, and support that a normal physiological effect of insulin in the enterocytes is the regulation of glucose metabolism.

<b><i>背景与目的：</i></b> 与链脲佐菌素（streptozotocin, STZ）诱导的糖尿病啮齿动物模型不同，目前尚无针对糖尿病遗传模型（如Zucker糖尿病肥胖（Zucker diabetic fatty, ZDF）大鼠）的肠道表型及其全基因表达谱潜在变化的系统性表征。本研究旨在对ZDF大鼠的肠道开展系统性表征。<b><i>方法：</i></b> 本研究从宏观与组织学层面检测ZDF大鼠与瘦型对照大鼠的肠道，并对空肠黏膜样本实施核糖核酸测序（RNAseq）分析。<b><i>结果：</i></b> 本研究观察到ZDF大鼠的小肠与大肠质量及长度均显著升高。RNAseq分析显示，空肠黏膜中参与糖脂代谢调控的*Pdk2*与*Pdk4*基因表达上调，同时糖异生及过氧化物酶体β-氧化相关基因的表达亦显著增加。<b><i>结论：</i></b> ZDF大鼠的肠道增大可能由进食量增加所介导，依据如下：其一，该表型同样见于肥胖且血糖正常的Zucker肥胖大鼠；其二，对链脲佐菌素诱导的糖尿病大鼠予以胰岛素治疗，可降低其进食量与小肠质量。RNAseq分析结果表明，ZDF大鼠的小肠上皮细胞已出现胰岛素抵抗，同时证实胰岛素在肠上皮细胞中的正常生理效应为调控葡萄糖代谢。