Dataset Information

Enriching Islet Phospholipids With Eicosapentaenoic Acid Reduces Prostaglandin E₂ Signaling and Enhances Diabetic ?-Cell Function.

ABSTRACT: Prostaglandin E₂ (PGE₂) is derived from arachidonic acid, whereas PGE₃ is derived from eicosapentaenoic acid (EPA) using the same downstream metabolic enzymes. Little is known about the impact of EPA and PGE₃ on ?-cell function, particularly in the diabetic state. In this work, we determined that PGE₃ elicits a 10-fold weaker reduction in glucose-stimulated insulin secretion through the EP3 receptor as compared with PGE₂ We tested the hypothesis that enriching pancreatic islet cell membranes with EPA, thereby reducing arachidonic acid abundance, would positively impact ?-cell function in the diabetic state. EPA-enriched islets isolated from diabetic BTBR Leptin^ob/ob mice produced significantly less PGE₂ and more PGE₃ than controls, correlating with improved glucose-stimulated insulin secretion. NAD(P)H fluorescence lifetime imaging showed that EPA acts downstream and independently of mitochondrial function. EPA treatment also reduced islet interleukin-1? expression, a proinflammatory cytokine known to stimulate prostaglandin production and EP3 expression. Finally, EPA feeding improved glucose tolerance and ?-cell function in a mouse model of diabetes that incorporates a strong immune phenotype: the NOD mouse. In sum, increasing pancreatic islet EPA abundance improves diabetic ?-cell function through both direct and indirect mechanisms that converge on reduced EP3 signaling.

SUBMITTER: Neuman JC

PROVIDER: S-EPMC5440023 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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Publications

Enriching Islet Phospholipids With Eicosapentaenoic Acid Reduces Prostaglandin E2 Signaling and Enhances Diabetic β-Cell Function.

Neuman Joshua C JC Schaid Michael D MD Brill Allison L AL Fenske Rachel J RJ Kibbe Carly R CR Fontaine Danielle A DA Sdao Sophia M SM Brar Harpreet K HK Connors Kelsey M KM Wienkes Haley N HN Eliceiri Kevin W KW Merrins Matthew J MJ Davis Dawn B DB Kimple Michelle E ME

Diabetes 20170213 6

Prostaglandin E2 (PGE2) is derived from arachidonic acid, whereas PGE3 is derived from eicosapentaenoic acid (EPA) using the same downstream metabolic enzymes. Little is known about the impact of EPA and PGE3 on β-cell function, particularly in the diabetic state. In this work, we determined that PGE3 elicits a 10-fold weaker reduction in glucose-stimulated insulin secretion through the EP3 receptor as compared with PGE2 We tested ...[more]

PMID: 28193789

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Project description:Asthma is characterized by chronic lung inflammation and airway hyperresponsiveness. Despite recent advances in the understanding of its pathophysiology, asthma remains a major public health problem and, at present, there are no effective interventions capable of reversing airway remodeling. Mesenchymal stromal cell (MSC)-based therapy mitigates lung inflammation in experimental allergic asthma; however, its ability to reduce airway remodeling is limited. We aimed to investigate whether pre-treatment with eicosapentaenoic acid (EPA) potentiates the therapeutic properties of MSCs in experimental allergic asthma. Seventy-two C57BL/6 mice were used. House dust mite (HDM) extract was intranasally administered to induce severe allergic asthma in mice. Unstimulated or EPA-stimulated MSCs were administered intratracheally 24 h after final HDM challenge. Lung mechanics, histology, protein levels of biomarkers, and cellularity in bronchoalveolar lavage fluid (BALF), thymus, lymph nodes, and bone marrow were analyzed. Furthermore, the effects of EPA on lipid body formation and secretion of resolvin-D1 (RvD1), prostaglandin E2 (PGE2), interleukin (IL)-10, and transforming growth factor (TGF)-β1 by MSCs were evaluated in vitro. EPA-stimulated MSCs, compared to unstimulated MSCs, yielded greater therapeutic effects by further reducing bronchoconstriction, alveolar collapse, total cell counts (in BALF, bone marrow, and lymph nodes), and collagen fiber content in airways, while increasing IL-10 levels in BALF and M2 macrophage counts in lungs. In conclusion, EPA potentiated MSC-based therapy in experimental allergic asthma, leading to increased secretion of pro-resolution and anti-inflammatory mediators (RvD1, PGE2, IL-10, and TGF-β), modulation of macrophages toward an anti-inflammatory phenotype, and reduction in the remodeling process. Taken together, these modifications may explain the greater improvement in lung mechanics obtained. This may be a promising novel strategy to potentiate MSCs effects.

Dataset Information

Enriching Islet Phospholipids With Eicosapentaenoic Acid Reduces Prostaglandin E₂ Signaling and Enhances Diabetic ?-Cell Function.

Publications

Enriching Islet Phospholipids With Eicosapentaenoic Acid Reduces Prostaglandin E<sub>2</sub> Signaling and Enhances Diabetic β-Cell Function.

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OmicsDI is part of the ELIXIR infrastructure

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Dataset Information

Enriching Islet Phospholipids With Eicosapentaenoic Acid Reduces Prostaglandin E2 Signaling and Enhances Diabetic ?-Cell Function.

Publications

Enriching Islet Phospholipids With Eicosapentaenoic Acid Reduces Prostaglandin E<sub>2</sub> Signaling and Enhances Diabetic β-Cell Function.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Enriching Islet Phospholipids With Eicosapentaenoic Acid Reduces Prostaglandin E₂ Signaling and Enhances Diabetic ?-Cell Function.