Ma Rui, Deng Xiao-Long, Aleteng Qi-Qi-Ge, Li Lei, Zhu Jun
Department of Endocrinology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, 830054, People's Republic of China.
Department of Endocrinology, Shunde Hospital of Southern Medical University, Foshan, Guangdong, 528300, People's Republic of China.
Diabetes Metab Syndr Obes. 2022 Jun 9;15:1761-1770. doi: 10.2147/DMSO.S334144. eCollection 2022.
In this study, transcriptome sequencing was performed on patients with type 2 diabetes mellitus treated with different prognosis to explore the differential level genes of different hypoglycemic effects of sitagliptin.
Patients with newly diagnosed T2DM (within six months of diagnosis) were selected as the study subjects. Patients were given sitagliptin 100 mg once a day orally. After 12 weeks of regular drug therapy, the reduction in glycated hemoglobin was compared before and after drug administration. The patients were then divided into two groups: the significantly effective group (M) and the less effective group (N). High-throughput sequencing of the transcriptome was conducted to detect the differential expression levels of genes in peripheral blood mononuclear cells. Expanded sample size validation of the candidate differential genes was conducted using reverse transcription-polymerase chain reaction (RT-PCR).
After 12 weeks of treatment with sitagliptin, high-throughput sequencing of the transcriptome found that expression of the following genes was different when comparing the significantly effective group (M) and the less effective group (N): ghrelin (), insulin-like growth factor-1 receptor (), mitogen-activated protein kinase-3 (), phosphatidylinositol-4,5-bisphosphonate 3-kinase, catalytic subunit delta (), and the suppressor of cytokine signaling-3 (). The validation results of RT-PCR showed that, in the significantly effective group (M), the expression of IGF1R was significantly increased ( = 0.034), the expression of was significantly reduced ( = 0.002), and the expression of was also significantly reduced ( < 0.001).
There was a significant difference in gene level between patients with significant hypoglycemic effect and patients with poor hypoglycemic effect, and the expression of IGF1R increased and the expression of MAPK3 and SOCS3 decreased.
本研究对接受不同预后治疗的2型糖尿病患者进行转录组测序，以探索西他列汀不同降糖效果的差异水平基因。
选取新诊断的2型糖尿病患者（诊断后6个月内）作为研究对象。患者口服西他列汀100mg，每日1次。经过12周的规律药物治疗后，比较给药前后糖化血红蛋白的降低情况。然后将患者分为两组：显效组（M）和疗效欠佳组（N）。对转录组进行高通量测序，以检测外周血单个核细胞中基因的差异表达水平。使用逆转录-聚合酶链反应（RT-PCR）对候选差异基因进行扩大样本量验证。
西他列汀治疗12周后，转录组高通量测序发现，比较显效组（M）和疗效欠佳组（N）时，以下基因的表达存在差异：胃饥饿素（）、胰岛素样生长因子-1受体（）、丝裂原活化蛋白激酶-3（）、磷脂酰肌醇-4,5-二磷酸3-激酶催化亚基δ（）和细胞因子信号转导抑制因子-3（）。RT-PCR验证结果显示，在显效组（M）中，IGF1R的表达显著增加（=0.034），的表达显著降低（=0.002），的表达也显著降低（<0.001）。
降糖效果显著的患者与降糖效果不佳的患者在基因水平上存在显著差异，IGF1R表达增加，MAPK3和SOCS3表达降低。
