4.8 Article

Tetrahedral Framework Nucleic Acids Ameliorate Insulin Resistance in Type 2 Diabetes Mellitus via the PI3K/Akt Pathway

期刊

ACS APPLIED MATERIALS & INTERFACES
卷 13, 期 34, 页码 40354-40364

出版社

AMER CHEMICAL SOC
DOI: 10.1021/acsami.1c11468

关键词

tetrahedral framework nucleic acids; insulin resistance; hepatocyte; type 2 diabetes mellitus; PI3K/Akt signaling pathway

资金

  1. National Key R&D Program of China [2019YFA0110600]
  2. National Natural Science Foundation of China [81970916, 81671031]
  3. Sichuan University postdoctoral interdisciplinary Innovation Fund

向作者/读者索取更多资源

The study demonstrates that tFNAs can improve hepatic insulin resistance by activating the IRS-1/PI3K/Akt pathway, leading to increased glucose uptake, promoted hepatic cell proliferation, reduced cell apoptosis, and lowered blood glucose levels in a T2DM mouse model. This highlights the potential application of tFNAs in improving T2DM through the PI3K/Akt pathway.
Insulin resistance (IR) is one of the essential conditions in the development of type 2 diabetes mellitus (T2DM). IR occurs in hepatic cells when the insulin receptor substrate-1 (IRS-1)/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway is downregulated; thus, activating this pathway can significantly improve insulin sensitivity and ameliorate T2DM. Tetrahedral framework nucleic acids (tFNAs), a DNA nanomaterial, are synthesized from four single-stranded DNA molecules. tFNAs possess excellent biocompatibility and good water solubility and stability. tFNAs can promote cell proliferation, cell autophagy, wound healing, and nerve regeneration by activating the PI3K/Akt pathway. Herein, we explore the effects and underlying mechanisms of tFNAs on IR. The results displayed that tFNAs could increase glucose uptake and ameliorate IR by activating the IRS-1/PI3K/Akt pathway in glucosamine (GlcN)-stimulated HepG2 cells. By employing a PI3K inhibitor, we confirmed that tFNAs reduce IR through the PI3K/Akt pathway. Moreover, tFNAs can promote hepatic cell proliferation and inhibit GlcN-induced cell apoptosis. In a T2DM mouse model, tFNAs reduce blood glucose levels and ameliorate hepatic IR via the PI3K/Akt pathway. Taken together, tFNAs can improve hepatic IR and alleviate T2DM through the PI3K/Akt pathway, making contribution to the potential application of tFNAs in T2DM.

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