| First Author | Yekollu SK | Year | 2011 |
| Journal | Diabetes | Volume | 60 |
| Issue | 11 | Pages | 2928-38 |
| PubMed ID | 21885868 | Mgi Jnum | J:189374 |
| Mgi Id | MGI:5445450 | Doi | 10.2337/db11-0275 |
| Citation | Yekollu SK, et al. (2011) Targeting curcusomes to inflammatory dendritic cells inhibits NF-kappaB and improves insulin resistance in obese mice. Diabetes 60(11):2928-38 |
| abstractText | OBJECTIVE: To determine whether and by what mechanism systemic delivery of curcumin-containing liposomes improves insulin resistance in the leptin deficient (ob/ob) mouse model of insulin resistance. RESEARCH DESIGN AND METHODS: Insulin resistant ob/ob mice with steatosis were injected intraperitoneally with liposome nanoparticles, entrapping the nuclear factor-kappaB (NF-kappaB) inhibitor curcumin (curcusomes), and uptake in liver and adipose tissue was determined by flow cytometry. The effects of curcusomes on macrophage NF-kappaB activation and cytokine production were assessed. Transfer experiments determined the role of hepatic tumor necrosis factor (TNF)/inducible nitric oxide synthase-producing dendritic cells (Tip-DCs) and adipose tissue macrophages (ATMs) in inflammation-induced insulin resistance, determined by homeostatic assessment of insulin resistance. RESULTS: Phagocytic myeloid cells infiltrating the liver in ob/ob mice had the phenotypic characteristics of Tip-DCs that arise from monocyte precursors in the liver and spleen after infection. Targeting Tip-DCs and ATMs with curcusomes in ob/ob mice reduced NF-kappaB/RelA DNA binding activity, reduced TNF, and enhanced interleukin-4 production. Curcusomes improved peripheral insulin resistance. CONCLUSIONS: Both hepatic Tip-DCs and ATMs contribute to insulin resistance in ob/ob mice. Curcusome nanoparticles inhibit proinflammatory pathways in hepatic Tip-DCs and ATMs and reverse insulin resistance. Targeting inflammatory DCs is a novel approach for type 2 diabetes treatment. |
