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Prostaglandin E 2 EP3 receptor modulation of insulin secretion in diabetes
Author(s) -
Ceddia Ryan P,
Gan Maureen,
Breyer Richard M.
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1169.19
Subject(s) - endocrinology , medicine , islet , insulin resistance , prostaglandin e , type 2 diabetes , insulin , ex vivo , prostaglandin e2 , diabetes mellitus , prostaglandin e2 receptor , glycemic , prostaglandin , receptor , in vivo , biology , agonist , microbiology and biotechnology
Prostaglandin E 2 (PGE 2 ) impairs glucose stimulated insulin secretion (GSIS) through its cognate G‐protein coupled receptors (GPCRs). Inhibition of EP3, the predominant PGE 2 GPCR in the pancreas, was investigated as a means of improving islet function and diabetic phenotype. The role of PGE 2 and EP3 in GSIS was assessed ex vivo with static islet culture utilizing EP3 antagonist, DG‐041, and islets from EP3 −/− mice. EP3 blockade improved GSIS in the presence of PGE 2 . Wild type (WT) and EP3 −/− animals on control feed had similar body weights and glucose tolerance. A high‐fat diet (HFD)‐fed model of type 2 diabetes was used to investigate the effects of EP3 inhibition in vivo . Acute DG‐041 administration to WT mice on HFD improved glucose clearance. When place on a HFD, EP3 −/− animals gained more weight and developed more severe insulin resistance than did WT mice. EP3 −/− mice on HFD had impaired glucose handling compared to WT. These results suggest that acute EP3 blockade improves glycemic control by increasing GSIS, while chronic global EP3 deletion increased obesity and insulin resistance. Funding for research was provided by a grant from the NIH, DK37097.