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Activation of G protein-coupled receptor 30 modulates hormone secretion and counteracts cytokine-induced apoptosis in pancreatic islets of female mice.

Balhuizen, Alexander LU ; Kumar, Rajesh LU ; Amisten, Stefan LU ; Lundquist, Ingmar LU and Salehi, S Albert LU (2010) In Molecular and Cellular Endocrinology 320. p.16-24
Abstract
The role of the newly discovered estrogen receptor GPR30 in islet physiology and pathophysiology is unclear. We examined GPR30 expression in relation to hormone secretion and possible anti-apoptotic effects in isolated mouse islets using the synthetic GPR30 ligand G-1. The mRNA and protein expression of GPR30 was analyzed by qPCR, Western blot and confocal microscopy. Hormone secretion and cAMP content were determined with RIA and apoptosis in islet cells with the Annexin-V method. GPR30 mRNA and protein expression was markedly higher in islets from females compared to male. This gender difference was not found for the genomic estrogen receptors ERalpha and ERbeta, the ERalpha expression being 10-fold higher than ERbeta in both genders.... (More)
The role of the newly discovered estrogen receptor GPR30 in islet physiology and pathophysiology is unclear. We examined GPR30 expression in relation to hormone secretion and possible anti-apoptotic effects in isolated mouse islets using the synthetic GPR30 ligand G-1. The mRNA and protein expression of GPR30 was analyzed by qPCR, Western blot and confocal microscopy. Hormone secretion and cAMP content were determined with RIA and apoptosis in islet cells with the Annexin-V method. GPR30 mRNA and protein expression was markedly higher in islets from females compared to male. This gender difference was not found for the genomic estrogen receptors ERalpha and ERbeta, the ERalpha expression being 10-fold higher than ERbeta in both genders. Confocal microscopy revealed abounden GPR30 expression in insulin, glucagon and somatostatin cells. Dose-response studies of G-1 vs 17beta-estradiol in isolated islets at 1 or 12mM glucose showed an almost identical pattern in that both compounds increased insulin and inhibited glucagon and somatostatin secretion. ICI-182,780 and EM-652, potent antagonists of the 17beta-estradiol receptors (ERalpha and ERbeta) did not influence the amplifying effect of G-1 or 17beta-estradiol on cAMP content or insulin secretion from isolated islets. Cytokine-induced (IL-1beta+TNFalpha+INFgamma) apoptosis in islets, cultured for 24h at 5mM glucose, was almost abolished by G-1 or 17beta-estradiol treatment. Addition of ICI-182,780 or EM-652 did not affect this beneficial effect of G-1 or 17beta-estradiol. Taken together, our findings show that GPR30 is expressed in most islet endocrine cells. The synthetic GPR30 ligand G-1 mimics the non-genomic effects of 17beta-estradiol on islet hormone secretion, cAMP content in islets and its anti-apoptotic effects. G-1 or analogs thereof might be new potential candidates in the therapeutic strategy for type 2 diabetes in women. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Molecular and Cellular Endocrinology
volume
320
pages
16 - 24
publisher
Elsevier
external identifiers
  • wos:000277066600002
  • pmid:20122988
  • scopus:77949566651
ISSN
1872-8057
DOI
10.1016/j.mce.2010.01.030
language
English
LU publication?
yes
id
038e4468-ceef-4388-ba4d-03ee6f72e61b (old id 1553054)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/20122988?dopt=Abstract
date added to LUP
2010-03-02 15:46:46
date last changed
2018-06-17 04:55:48
@article{038e4468-ceef-4388-ba4d-03ee6f72e61b,
  abstract     = {The role of the newly discovered estrogen receptor GPR30 in islet physiology and pathophysiology is unclear. We examined GPR30 expression in relation to hormone secretion and possible anti-apoptotic effects in isolated mouse islets using the synthetic GPR30 ligand G-1. The mRNA and protein expression of GPR30 was analyzed by qPCR, Western blot and confocal microscopy. Hormone secretion and cAMP content were determined with RIA and apoptosis in islet cells with the Annexin-V method. GPR30 mRNA and protein expression was markedly higher in islets from females compared to male. This gender difference was not found for the genomic estrogen receptors ERalpha and ERbeta, the ERalpha expression being 10-fold higher than ERbeta in both genders. Confocal microscopy revealed abounden GPR30 expression in insulin, glucagon and somatostatin cells. Dose-response studies of G-1 vs 17beta-estradiol in isolated islets at 1 or 12mM glucose showed an almost identical pattern in that both compounds increased insulin and inhibited glucagon and somatostatin secretion. ICI-182,780 and EM-652, potent antagonists of the 17beta-estradiol receptors (ERalpha and ERbeta) did not influence the amplifying effect of G-1 or 17beta-estradiol on cAMP content or insulin secretion from isolated islets. Cytokine-induced (IL-1beta+TNFalpha+INFgamma) apoptosis in islets, cultured for 24h at 5mM glucose, was almost abolished by G-1 or 17beta-estradiol treatment. Addition of ICI-182,780 or EM-652 did not affect this beneficial effect of G-1 or 17beta-estradiol. Taken together, our findings show that GPR30 is expressed in most islet endocrine cells. The synthetic GPR30 ligand G-1 mimics the non-genomic effects of 17beta-estradiol on islet hormone secretion, cAMP content in islets and its anti-apoptotic effects. G-1 or analogs thereof might be new potential candidates in the therapeutic strategy for type 2 diabetes in women.},
  author       = {Balhuizen, Alexander and Kumar, Rajesh and Amisten, Stefan and Lundquist, Ingmar and Salehi, S Albert},
  issn         = {1872-8057},
  language     = {eng},
  pages        = {16--24},
  publisher    = {Elsevier},
  series       = {Molecular and Cellular Endocrinology},
  title        = {Activation of G protein-coupled receptor 30 modulates hormone secretion and counteracts cytokine-induced apoptosis in pancreatic islets of female mice.},
  url          = {http://dx.doi.org/10.1016/j.mce.2010.01.030},
  volume       = {320},
  year         = {2010},
}