Gα z -independent and -dependent Improvements With EPA Supplementation on the Early Type 1 Diabetes Phenotype of NOD Mice.

Autor: Fenske RJ; Research Service, William S. Middleton Memorial VA Hospital, Madison, WI 53705, USA.; Department of Nutritional Sciences, University of Wisconsin-Madison, Madison, WI 53706, USA.; Clinical Research Unit, University of Wisconsin Hospitals and Clinics, Madison, WI 53792, USA., Wienkes HN; Research Service, William S. Middleton Memorial VA Hospital, Madison, WI 53705, USA.; Department of Medicine, University of Wisconsin-Madison, Madison, WI 53705, USA., Peter DC; Research Service, William S. Middleton Memorial VA Hospital, Madison, WI 53705, USA.; Department of Medicine, University of Wisconsin-Madison, Madison, WI 53705, USA., Schaid MD; Research Service, William S. Middleton Memorial VA Hospital, Madison, WI 53705, USA.; Department of Nutritional Sciences, University of Wisconsin-Madison, Madison, WI 53706, USA.; Department of Medicine, University of Wisconsin-Madison, Madison, WI 53705, USA., Hurley LD; Research Service, William S. Middleton Memorial VA Hospital, Madison, WI 53705, USA.; Department of Medicine, University of Wisconsin-Madison, Madison, WI 53705, USA., Pennati A; Department of Medicine, University of Wisconsin-Madison, Madison, WI 53705, USA.; University of Wisconsin Carbone Cancer Center, University of Wisconsin-Madison, Madison, WI 53705, USA., Galipeau J; Department of Medicine, University of Wisconsin-Madison, Madison, WI 53705, USA.; University of Wisconsin Carbone Cancer Center, University of Wisconsin-Madison, Madison, WI 53705, USA., Kimple ME; Research Service, William S. Middleton Memorial VA Hospital, Madison, WI 53705, USA.; Department of Medicine, University of Wisconsin-Madison, Madison, WI 53705, USA.; Department of Cell and Regenerative Biology, University of Wisconsin-Madison, Madison, WI 53705, USA.
Jazyk: angličtina
Zdroj: Journal of the Endocrine Society [J Endocr Soc] 2024 May 21; Vol. 8 (7), pp. bvae100. Date of Electronic Publication: 2024 May 21 (Print Publication: 2024).
DOI: 10.1210/jendso/bvae100
Abstrakt: Prostaglandin E 2 (PGE 2 ) is a key mediator of inflammation and is derived from the omega-6 polyunsaturated fatty acid, arachidonic acid (AA). In the β-cell, the PGE 2 receptor, Prostaglandin EP3 receptor (EP3), is coupled to the unique heterotrimeric G protein alpha subunit, Gɑ z to reduce the production of cyclic adenosine monophosphate (cAMP), a key signaling molecule that activates β-cell function, proliferation, and survival pathways. Nonobese diabetic (NOD) mice are a strong model of type 1 diabetes (T1D), and NOD mice lacking Gɑ z are protected from hyperglycemia. Therefore, limiting systemic PGE 2 production could potentially improve both the inflammatory and β-cell dysfunction phenotype of T1D. Here, we sought to evaluate the effect of eicosapentaenoic acid (EPA) feeding, which limits PGE 2 production, on the early T1D phenotype of NOD mice in the presence and absence of Gα z . Wild-type and Gα z knockout NOD mice were fed a control or EPA-enriched diet for 12 weeks, beginning at age 4 to 5 weeks. Oral glucose tolerance, splenic T-cell populations, islet cytokine/chemokine gene expression, islet insulitis, measurements of β-cell mass, and measurements of β-cell function were quantified. EPA diet feeding and Gɑ z loss independently improved different aspects of the early NOD T1D phenotype and coordinated to alter the expression of certain cytokine/chemokine genes and enhance incretin-potentiated insulin secretion. Our results shed critical light on the Gα z -dependent and -independent effects of dietary EPA enrichment and provide a rationale for future research into novel pharmacological and dietary adjuvant therapies for T1D.
(Published by Oxford University Press on behalf of the Endocrine Society 2024.)
Databáze: MEDLINE
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