Project description:Insulin receptor (IR) signaling is central to normal metabolic control and is dysregulated in metabolic diseases such as type 2 diabetes. We report here that IR is incorporated into dynamic clusters at the plasma membrane, in the cytoplasm and in the nucleus of human hepatocytes and adipocytes. Insulin stimulation promotes further incorporation of IR into these dynamic clusters in insulin-sensitive cells but not in insulin-resistant cells, where both IR accumulation and dynamic behavior are reduced. Treatment of insulin-resistant cells with metformin, a first-line drug used to treat type 2 diabetes, can rescue IR accumulation and the dynamic behavior of these clusters. This rescue is associated with metformin’s role in reducing reactive oxygen species that interfere with normal dynamics. These results indicate that changes in the physico-mechanical features of IR clusters contribute to insulin resistance and have implications for improved therapeutic approaches.
Project description:There is evidence indicating the involvement of DNA methylation memory in maintaining gene expression patterns associated with insulin resistance. Although the exact mechanism remains unknown, it has been proved that insulin resistance is correlated to low heat shock protein (HSP) expression. We reveal that intranuclear insulin can reduce HSP DNA methylation level to up-regulate HSP protein expression and result in long term cure of hyperglycemia. Insulin resistance HepG2 cell were selected in our experiments.Two conditions were compared with three replicates each. These are:(1) Insulin resistance HepG2(R-HepG2) and (2) Biomineralized insulin treated HepG2 (BI).
Project description:There is evidence indicating the involvement of DNA methylation memory in maintaining gene expression patterns associated with insulin resistance. Although the exact mechanism remains unknown, it has been proved that insulin resistance is correlated to low heat shock protein (HSP) expression. We reveal that intranuclear insulin can reduce HSP DNA methylation level to up-regulate HSP protein expression and result in long term cure of hyperglycemia. Insulin resistance HepG2 cell were selected in our experiments.Three conditions were compared with three replicates each. These are:(1) Insulin resistance HepG2(R-HepG2) (2) Insulin treated HepG2(Insulin); (3) Biomineralized insulin treated HepG2 (BI).
Project description:This project contains proteomic data obtained from the soleus muscle of mice subjected to a high-fat diet (HFD) for ten weeks. The experiment included FAM3A-transgenic mice (n=6) and wild-type controls (n=6). The data aim to explore the role of FAM3A in skeletal muscle adaptation to HFD and metabolic stress.
Project description:Insulin resistance (IR) is likely to induce metabolic syndrome and type 2 diabetes mellitus (T2DM). Gluconeogenesis (GNG) is a complex metabolic process that may result in glucose generation from certain non-carbohydrate substrates. Chinese herbal medicine astragalus polysaccharides and berberine have been documented to ameliorate IR, and combined use of astragalus polysaccharide (AP) and berberine (BBR) are reported to synergistically produce an even better effect. However, what change may occur in the GNG signaling pathway of IR-HepG2 cells in this synergistic effect and whether AP-BBR attenuates IR by regulating the GNG signaling pathway remain unclear. For the first time, we discovered in this study that the optimal time of IR-HepG2 cell model formation was 48 hours after insulin intervention. AP-BBR attenuated IR in HepG2 cells and the optimal concentration was 10mg. AP-BBR reduced the intracellular H2O2 content with no significant effect on apoptosis of IR-HepG2 cells. In addition, a rapid change was observed in intracellular calcium current of the IR-HepG2 cell model, and AP-BBR intervention attenuated this change markedly. The gene sequencing results showed that the GNG signaling pathway was one of the signaling pathways of AP-BBR to attenuate IR in IR-Hepg2 cells. The expression of p-FoxO1Ser256 and PEPCK protein was increased and the expression of GLUT2 protein was decreased significantly in the IR-HepG2 cell model, and both of these effects could be reversed by AP-BBR intervention. AP-BBR attenuated IR in IR-HepG2 cells, probably by regulating the GNG signaling Pathway.