六个肥胖相关基因在食蟹猴2型糖尿病不同发病时期的差异表达

2型糖尿病(T2DM)是一种与基因密切相关的高发性代谢性疾病。采用高脂饮食(其中含15%猪油)喂养25只中老年雄性食蟹猴的方法,制备T2DM模型,通过检测血糖与血脂水平确定疾病发展进程,并利用实时PCR对外周血白细胞中的6个肥胖相关基因mRNA表达量进行测定。食蟹猴T2DM在临床前期和临床期口服糖耐量实验(OGTT)2-h血糖值分别为(11.06±6.05)mmol/L和(13.12±2.89)mmol/L,显著高于正常组;空腹血糖在临床期达到最大值,为(7.58±1.56)mmol/L(P<0.01),说明其T2DM模型被成功诱导。但所检测的6个糖尿病肥胖相关基因中只有CDKN2B、IGF2BP2和FTOmRNA表达量与糖尿病发病进程呈正相关,且临床期IGF2BP2和FTO的表达量分别是对照组的65.92倍和4.30倍,差异极显著(P<0.01)。因此,基因CDKN2B、IGF2BP2和FTO可作为食蟹猴糖尿病早期诊断及预后评价的参考指标。

Differential expression of six obesity-related genes with different disease phases of T2DM in cynomolgus monkey

Type 2 diabetes mellitus (T2DM) is a metabolic disease with a strong genetic component that is very prevalent in the world. The aim of this study is to investigate the association of a set of six obesity-related genes with the different disease phases of T2DMin a model using middle or aged cynomogus monkeys. A total of 25 male monkeys were used and fed with high-fat diet (15% lard). The disease development and progression of T2DM were monitored through the levels of plasma glucose and lipid. The mRNA expression of 6 genes was evaluated using real-time PCR on monocyte isolated from monkey peripheral blood. The 2-hour plasma glucose levels followed oral glucose tolerance test (OGTT) were (11.06±6.05) mmol/L and (13.12±2.89) mmol/L respectively (P<0.01), and the fasting plasma glucose level was (7.58±1.56) mmol/L (vs controls, P<0.01), indicating that we developed successful the models of pre-diabetic and diabetic disease in the cynomolgus monkey. Of the six tested genes, CDKN2B, IGF2BP2, and FTO genes were significantly up-regulated with disease progression in T2DM. We found that the expression of IGF2BP2 and FTO increased 65.92 and 4.30 folds in the developed T2DM. We conclude that the genes of CDKN2B, IGF2BP2, and FTO can be used as early diagnostic and prognostic biomarkers in type 2 diabetes.