National Agri-Food Biotechnology Institute (NABI), Sector-81, S.A.S Nagar, Mohali 140306, Punjab, India; Department of Biotechnology, Panjab University, Sector 25, Chandigarh 160014, India.
National Institute for Implementation Research on Non-Communicable Diseases, Jodhpur 342005, India.
Int J Biol Macromol. 2024 Jun;270(Pt 2):132504. doi: 10.1016/j.ijbiomac.2024.132504. Epub 2024 May 20.
It is well-accepted that the liver plays a vital role in the metabolism of glucose and its homeostasis. Dysregulated hepatic glucose production and utilization, leads to type 2 diabetes (T2DM). In the current study, RNA sequencing and qRT-PCR analysis of nanoformulation-treated T2DM mice (TG group) revealed beneficial crosstalk of PCK-1 silencing with other pathways involved in T2DM. The comparison of precise genetic expression profiles of the different experimental groups showed significantly improved hepatic glucose, fatty acid metabolism and several other T2DM-associated crucial markers after the nanoformulation treatment. As a result of these improvements, we observed a significant acceleration in wound healing and improved insulin signaling in vascular endothelial cells in the TG group as compared to the T2DM group. Enhanced phosphorylation of PI3K/Akt pathway proteins in the TG group resulted in increased angiogenesis as observed by the increased expression of endothelial cell markers (CD31, CD34) thereby improving endothelial dysfunctions in the TG group. Additionally, therapeutic nanoformulation has been observed to improve the inflammatory cytokine profile in the TG group. Overall, our results demonstrated that the synthesized therapeutic nanoformulation referred to as GPR8:PCK-1 holds the potential in ameliorating hyperglycemia-associated complications such as delayed wound healing in diabetes.
人们普遍认为，肝脏在葡萄糖代谢及其稳态中起着至关重要的作用。肝葡萄糖生成和利用的失调会导致 2 型糖尿病（T2DM）。在本研究中，对纳米制剂治疗的 T2DM 小鼠（TG 组）进行 RNA 测序和 qRT-PCR 分析，揭示了 PCK-1 沉默与其他参与 T2DM 的途径之间有益的串扰。对不同实验组的精确基因表达谱进行比较后发现，纳米制剂治疗后，肝脏葡萄糖、脂肪酸代谢和其他几个与 T2DM 相关的关键标志物均得到显著改善。由于这些改善，我们观察到 TG 组的伤口愈合明显加快，血管内皮细胞中的胰岛素信号转导得到改善。TG 组中 PI3K/Akt 通路蛋白的磷酸化增强导致血管生成增加，内皮细胞标志物（CD31、CD34）的表达增加，从而改善了 TG 组的内皮功能障碍。此外，治疗性纳米制剂被观察到可改善 TG 组中的炎症细胞因子谱。总的来说，我们的结果表明，所合成的治疗性纳米制剂 GPR8:PCK-1 具有改善与高血糖相关的并发症的潜力，例如糖尿病患者的伤口愈合延迟。
