@article {Srivastava2023-cd,
	title = {Posttranscriptional regulation of the prostaglandin E receptor spliced-isoform EP3-\&gamma; and its implication in pancreatic \&beta;-cell failure},
	journal = {FASEB J.},
	volume = {37},
	number = {6},
	year = {2023},
	pages = {e22958},
	abstract = {In Type 2 diabetes (T2D), elevated lipid levels have been suggested to contribute to insulin resistance and β-cell dysfunction. We previously reported that the expression of the PGE2 receptor EP3 is elevated in islets of T2D individuals and is preferentially stimulated by palmitate, leading to β-cell failure. The mouse EP3 receptor generates three isoforms by alternative splicing which differ in their C-terminal domain and are referred to as mEP3α, mEP3β, and mEP3γ. We bring evidence that the expression of the mEP3γ isoform is elevated in islets of diabetic db/db mice and is selectively upregulated by palmitate. Specific knockdown of the mEP3γ isoform restores the expression of β-cell-specific genes and rescues MIN6 cells from palmitate-induced dysfunction and apoptosis. This study indicates that palmitate stimulates the expression of the mEP3γ by a posttranscriptional mechanism, compared to the other spliced isoforms, and that the de novo synthesized ceramide plays an important role in FFA-induced mEP3γ expression in β-cells. Moreover, induced levels of mEP3γ mRNA by palmitate or ceramide depend on p38 MAPK activation. Our findings suggest that mEP3γ gene expression is regulated at the posttranscriptional level and defines the EP3 signaling axis as an important pathway mediating β-cell-impaired function and demise.},
	keywords = {Apoptosis, beta cells, Diabetes Mellitus, free fatty acids, posttranscriptional regulation, PTGER3-EP3 receptor},
	author = {Srivastava, Rohit and Horwitz, Margalit and Hershko-Moshe, Anat and Bronstein, Shirly and Ben-Dov, Iddo Z and Melloul, Danielle}
}
