Endothelial differentiation gene receptors in pancreatic islets and INS-1 cells.
The endothelial differentiation gene (EDG) receptors are a class of G protein-coupled receptors. EDG-1, -3, -5, -6, and -8 bind the bioactive lipid sphingosine-1-phosphate (SPP) as the primary signaling ligand. EDG-2, -4, and -7 bind the ligand lysophosphatidic acid. EDG-1, -2, -3, -5, -6, and -7, but not -8, mRNAs were expressed in isolated rat pancreatic islets, whereas INS-1 insulinoma cells expressed only EDG-1, -2, -3, and -5 mRNAs. EDG-4 mRNA was expressed in mouse islets. EDG-1 mRNA but not EDG-3 mRNA was rapidly induced relative to 18S rRNA after stimulation of isolated islets with phorbol 12-myristate 13-acetate (PMA) or cholecystokinin-8S for 2 h. The protein kinase C inhibitor GF 109203X blocked the EDG-1 induction by PMA. Similarly, in islets stimulated for 2 h with 17 mmol/l glucose, the relative EDG-1 mRNA levels increased almost twofold compared with levels in control islets at 5.5 mmol/l glucose. In contrast, after 11 mmol/l glucose stimulation for 7 days, the relative levels of rat islet EDG-1 mRNA were significantly reduced to 54% below that of islets cultured at 5.5 mmol/l glucose. There was no change in relative EDG-3 mRNA levels. Stimulation of EDG receptors in islets and INS-1 cells with SPP inhibited glucagon-like peptide 1 (GLP-1)-stimulated cAMP production and insulin secretion in a concentration-dependent manner. Pertussis toxin antagonized the SPP effects on insulin release. Thus, EDG receptors are expressed in pancreatic islet beta-cells and G(i) seems to mediate the inhibition by SPP of adenylyl cyclase and cAMP formation and inhibition of the stimulation of insulin secretion by GLP-1.
Laychock
Suzanne G
SG
Department of Pharmacology and Toxicology, School of Medicine and Biomedical Sciences, the State University of New York at Buffalo, Buffalo, New York, USA. laychock@buffalo.edu
Tian
Yingrao
Y
Sessanna
Shawn M
SM
D000818:Animals; D002273:Carcinogens / Q000494:pharmacology; D002454:Cell Differentiation / Q000502:physiology; D002766:Cholecystokinin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D004727:Endothelium / Q000166:cytology; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000378:metabolism; D015870:Gene Expression / Q000502:physiology; D005947:Glucose / Q000494:pharmacology; D066298:In Vitro Techniques; D007340:Insulinoma; D007515:Islets of Langerhans / Q000166:cytology* / Q000502:physiology*; D008246:Lysophospholipids; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface / Q000235:genetics*; D043562:Receptors, G-Protein-Coupled; D049312:Receptors, Lysophospholipid; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D002273:Carcinogens; D008246:Lysophospholipids; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D049312:Receptors, Lysophospholipid; C060506:sphingosine 1-phosphate; D002766:Cholecystokinin; D000242:Cyclic AMP; D019205:GTP-Binding Protein alpha Subunits, Gs; D005947:Glucose; D013110:Sphingosine; D013755:Tetradecanoylphorbol Acetate