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Glucagon‐like Peptide‐1 (GLP‐1) Attenuates Agoniststimulated Cytosolic Free Calcium ([Ca2+]i) Signaling and the Production of F2α‐isoprostane in Endothelial Cells
Author(s) -
Richardson Vanitra A,
Weber Craig S,
Lynch Ronald M,
Dokken Betsy B
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.900.5
Subject(s) - endocrinology , medicine , glucagon like peptide 1 , umbilical vein , endothelium , endothelial dysfunction , chemistry , nitric oxide , proglucagon , vasodilation , type 2 diabetes , diabetes mellitus , in vitro , biochemistry
Endothelial dysfunction contributes to cardiovascular disease in diabetes. Glucagon‐like peptide‐1 (GLP‐1) is an incretin hormone that forms the basis of a class of drugs used to treat type 2 diabetes, but its effect on microvascular endothelium is largely unknown. F2α‐isoprostanes (F2αI) have vasoconstrictor properties and are produced in excess in diabetic endothelium. A rise in [Ca 2+ ] i is required for the free‐radical mediated synthesis of F2αI. In the present study, the Ca 2+ ‐sensitive dye Fura‐2 was used to evaluate the effect of GLP‐1 on the ATP‐induced [Ca 2+ ] i rise in human cardiac microvascular endothelial cells (HMVEC‐Cs). In addition, human umbilical vein endothelial cells (HUVECs) were exposed to GLP‐1 (0.3 nM) for 48 hr and the release of F2αI into the media was determined by enzyme immunoassay (EIA). GLP‐1 depressed the ATP‐induced elevation of [Ca 2+ ] i (109 ± 15 nM [control] vs. 44 ± 6 nM [GLP‐1], P <0.05) in HMVEC‐Cs, and also attenuated F2αI release by HUVECS (5.8 ± 0.1‐fold over baseline [control] vs. 3.6 ± 0.2‐fold over baseline [GLP‐1], P <0.05). These results suggest that GLP‐1 may improve endothelial function in diabetic patients, in part by decreasing the [Ca 2+ ] i –dependent release of F2αI, an endothelium‐dependent constricting factor. This study was supported by the University of Arizona Sarver Heart Center, and the Harold and Nancy Willingham Foundation.