Peng Miaoguan, Zhang Yingying, Weng Xiaoshi, Wu Jianfeng, Luo Taizhen, Dong Yanmei, Wen Shiyun, Liang Naifeng, Zhong Liangying, Zhai Yaojie, Xie Yijuan, Xie Yingjun, Chen Yuyi
Department of Endocrinology, Guangdong Provincial Key Laboratory of Major Obstetric Diseases, Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology, Guangdong-Hong Kong-Macao Greater Bay Area Higher Education Joint Laboratory of Maternal-Fetal Medicine, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou 510150, China.
Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, Guangzhou Medical University, Guangzhou 510170, China.
Biomedicines. 2025 Apr 17;13(4):980. doi: 10.3390/biomedicines13040980.
: Epigenetic regulation plays a critical role in diabetes research, with N6-methyladenosine (m6A) modification emerging as a key factor in disease progression. METTL14, an essential epigenetic regulator, may influence the effects of thiamine on intensive insulin therapy in diabetic patients. : Blood samples from twenty diabetic patients were collected before and after intensive insulin therapy for MeRIP-seq and RNA-seq analysis. Genes with m6A modifications and corresponding mRNAs were identified and functionally analyzed using Gene Ontology (GO) and KEGG pathway analysis. RT-qPCR was used to confirm the overexpression of METTL14, PIK3R1, TPK1, and IPMK, while METTL14 overexpression was further validated in THP1 cells. : GO analysis revealed a significant enrichment of overlapping genes in metabolic pathways. A reduction in m6A modification levels was observed post intensive insulin therapy, indicating METTL14's involvement in regulating TPK1, IPMK, and PIK3R1 expression. TPK1 levels showed a positive correlation with thiamine levels. Clinical validation demonstrated that combining thiamine with insulin therapy significantly reduced glucose and triglyceride levels compared to insulin alone. : Thiamine supplementation alongside intensive insulin therapy offers therapeutic potential by downregulating TPK1 expression and mitigating lipid-related complications in diabetic patients. These findings highlight the pivotal role of METTL14-mediated m6A modification in regulating key metabolic genes during diabetes treatment.
表观遗传调控在糖尿病研究中起着关键作用,N6-甲基腺苷(m6A)修饰已成为疾病进展的关键因素。METTL14是一种重要的表观遗传调节因子,可能影响硫胺素对糖尿病患者强化胰岛素治疗的效果。
收集20例糖尿病患者强化胰岛素治疗前后的血样进行MeRIP-seq和RNA-seq分析。使用基因本体论(GO)和KEGG通路分析鉴定具有m6A修饰的基因及其相应的mRNA,并进行功能分析。采用RT-qPCR法验证METTL14、PIK3R1、TPK1和IPMK的过表达,同时在THP1细胞中进一步验证METTL14的过表达。
GO分析显示代谢途径中的重叠基因显著富集。强化胰岛素治疗后观察到m6A修饰水平降低,表明METTL14参与调节TPK1、IPMK和PIK3R1的表达。TPK1水平与硫胺素水平呈正相关。临床验证表明,与单独使用胰岛素相比,硫胺素与胰岛素联合治疗可显著降低血糖和甘油三酯水平。
在强化胰岛素治疗的同时补充硫胺素,通过下调TPK1表达和减轻糖尿病患者的脂质相关并发症,具有治疗潜力。这些发现突出了METTL14介导的m6A修饰在糖尿病治疗过程中调节关键代谢基因的关键作用。