Linked Life Data

21521748

Source:http://linkedlifedata.com/resource/pubmed/id/21521748

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2011-6-23
pubmed:abstractText
We have recently shown that 17?-estradiol (E2) and the synthetic G protein-coupled receptor 30 (GPR30) ligand G-1 have antiapoptotic actions in mouse pancreatic islets, raising the prospect that they might exert beneficial effects also in human islets. The objective of the present study was to identify the expression of GPR30 in human islets and clarify the role of GPR30 in islet hormone secretion and ?-cell survival. GPR30 expression was analyzed by confocal microscopy, Western blot, and quantitative PCR in islets from female and male donors. Hormone secretion, phosphatidylinositol hydrolysis, cAMP content, and caspase-3 activity in female islets were determined with conventional methods and apoptosis with the annexin-V method. Confocal microscopy revealed GPR30 expression in islet insulin, glucagon, and somatostatin cells. GPR30 mRNA and protein expression was markedly higher in female vs. male islets. An amplifying effect of G-1 or E2 on cAMP content and insulin secretion from isolated female islets was not influenced by the E2 genomic receptor (ER? and ER?) antagonists ICI 182,780 and EM-652. Cytokine-induced (IL-1? plus TNF? plus interferon-?) apoptosis in islets cultured for 24 h at 5 mmol/liter glucose was almost abolished by G-1 or E2 treatment and was not affected by the nuclear estrogen receptor antagonists. Concentration-response studies on female islets from healthy controls and type 2 diabetic subjects showed that both E2 and G-1 displayed important antidiabetic actions by improving glucose-stimulated insulin release while suppressing glucagon and somatostatin secretion. In view of these findings, we propose that small molecules activating GPR30 could be promising in the therapy of diabetes mellitus.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1945-7170
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
152
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2568-79
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:21521748-Apoptosis, pubmed-meshheading:21521748-Cell Survival, pubmed-meshheading:21521748-Cyclopentanes, pubmed-meshheading:21521748-Diabetes Mellitus, Type 2, pubmed-meshheading:21521748-Estradiol, pubmed-meshheading:21521748-Estrogen Antagonists, pubmed-meshheading:21521748-Female, pubmed-meshheading:21521748-Gene Expression Regulation, pubmed-meshheading:21521748-Humans, pubmed-meshheading:21521748-Hyperglycemia, pubmed-meshheading:21521748-Hypoglycemic Agents, pubmed-meshheading:21521748-Insulin, pubmed-meshheading:21521748-Islets of Langerhans, pubmed-meshheading:21521748-Male, pubmed-meshheading:21521748-Molecular Targeted Therapy, pubmed-meshheading:21521748-Oligonucleotide Array Sequence Analysis, pubmed-meshheading:21521748-Organ Culture Techniques, pubmed-meshheading:21521748-Quinolines, pubmed-meshheading:21521748-RNA, Messenger, pubmed-meshheading:21521748-Receptors, Estrogen, pubmed-meshheading:21521748-Receptors, G-Protein-Coupled, pubmed-meshheading:21521748-Second Messenger Systems, pubmed-meshheading:21521748-Sex Characteristics
pubmed:year
2011
pubmed:articleTitle
Insulinotropic and antidiabetic effects of 17?-estradiol and the GPR30 agonist G-1 on human pancreatic islets.
pubmed:affiliation
Department of Clinical Science, Skåne Universitetssjukhus, Division of Islet Cell Physiology, Clinical Research Center, Building 91, Plan 11, Entrance 72, S-205 02 Malmö, Sweden.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't