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Targeting curcusomes to inflammatory dendritic cells inhibits NF-κB and improves insulin resistance in obese mice.

Yekollu SK, Thomas R, O'Sullivan B - Diabetes (2011)

Bottom Line: 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-κB/RelA DNA binding activity, reduced TNF, and enhanced interleukin-4 production.Targeting inflammatory DCs is a novel approach for type 2 diabetes treatment.

View Article: PubMed Central - PubMed

Affiliation: University of Queensland Diamantina Institute, Woolloongabba, Queensland, Australia.

ABSTRACT

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-κB (NF-κB) inhibitor curcumin (curcusomes), and uptake in liver and adipose tissue was determined by flow cytometry. The effects of curcusomes on macrophage NF-κB 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-κB/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.

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Related in: MedlinePlus

Improved insulin signaling in tissues isolated from ob/ob mice treated with curcusomes. Lysates of quadriceps and liver from curcusome-treated or untreated ob/ob mice signaled with (I) or without (S) insulin were analyzed by SDS-PAGE and immunoblotted for pAKT (ser473) and AKT. Induction of pAKT in NOB mice after insulin injection was used as a positive control for the experiment.
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Figure 5: Improved insulin signaling in tissues isolated from ob/ob mice treated with curcusomes. Lysates of quadriceps and liver from curcusome-treated or untreated ob/ob mice signaled with (I) or without (S) insulin were analyzed by SDS-PAGE and immunoblotted for pAKT (ser473) and AKT. Induction of pAKT in NOB mice after insulin injection was used as a positive control for the experiment.

Mentions: To assess tissue-specific effects on insulin signaling after curcusome treatment, fasted ob/ob mice, treated or untreated with curcusomes, were injected with insulin and pAKT levels were determined in the liver and skeletal tissue. Increased levels of insulin-induced pAKT were observed in the liver and skeletal muscle of ob/ob mice treated with curcusomes, indicating systemic improvements in insulin signaling after curcusome treatment (Fig. 5).


Targeting curcusomes to inflammatory dendritic cells inhibits NF-κB and improves insulin resistance in obese mice.

Yekollu SK, Thomas R, O'Sullivan B - Diabetes (2011)

Improved insulin signaling in tissues isolated from ob/ob mice treated with curcusomes. Lysates of quadriceps and liver from curcusome-treated or untreated ob/ob mice signaled with (I) or without (S) insulin were analyzed by SDS-PAGE and immunoblotted for pAKT (ser473) and AKT. Induction of pAKT in NOB mice after insulin injection was used as a positive control for the experiment.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3198103&req=5

Figure 5: Improved insulin signaling in tissues isolated from ob/ob mice treated with curcusomes. Lysates of quadriceps and liver from curcusome-treated or untreated ob/ob mice signaled with (I) or without (S) insulin were analyzed by SDS-PAGE and immunoblotted for pAKT (ser473) and AKT. Induction of pAKT in NOB mice after insulin injection was used as a positive control for the experiment.
Mentions: To assess tissue-specific effects on insulin signaling after curcusome treatment, fasted ob/ob mice, treated or untreated with curcusomes, were injected with insulin and pAKT levels were determined in the liver and skeletal tissue. Increased levels of insulin-induced pAKT were observed in the liver and skeletal muscle of ob/ob mice treated with curcusomes, indicating systemic improvements in insulin signaling after curcusome treatment (Fig. 5).

Bottom Line: 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-κB/RelA DNA binding activity, reduced TNF, and enhanced interleukin-4 production.Targeting inflammatory DCs is a novel approach for type 2 diabetes treatment.

View Article: PubMed Central - PubMed

Affiliation: University of Queensland Diamantina Institute, Woolloongabba, Queensland, Australia.

ABSTRACT

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-κB (NF-κB) inhibitor curcumin (curcusomes), and uptake in liver and adipose tissue was determined by flow cytometry. The effects of curcusomes on macrophage NF-κB 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-κB/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.

Show MeSH
Related in: MedlinePlus