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Uridine diphosphate (UDP) stimulates insulin secretion by activation of P2Y(6) receptors.

Parandeh, Fariborz; Abaraviciene, Sandra Meidute; Amisten, Stefan LU ; Erlinge, David LU and Salehi, S Albert LU (2008) In Biochemical and Biophysical Research Communications 6;370(3). p.499-503
Abstract
We examined the transcriptional expression and functional effects of receptors for the extracellular pyrimidines uridine triphosphate (UTP) and uridine diphosphate (UDP), on insulin and glucagon secretion in isolated mouse pancreatic islets and purified beta-cells. Using real-time PCR, the UDP receptor P2Y(6) was found to be highly expressed in both whole islets and beta-cells purified by repeated counter-flow elutriation, whereas no mRNA expression for UTP receptors P2Y(4) and P2Y(2) could be detected. Functional in vitro experiments revealed that the P2Y(6) agonist UDPbetaS dose-dependently enhanced insulin and glucagon release during short-term incubation (1h), while P2Y(6) activation during a longer period (24h), selectively increased... (More)
We examined the transcriptional expression and functional effects of receptors for the extracellular pyrimidines uridine triphosphate (UTP) and uridine diphosphate (UDP), on insulin and glucagon secretion in isolated mouse pancreatic islets and purified beta-cells. Using real-time PCR, the UDP receptor P2Y(6) was found to be highly expressed in both whole islets and beta-cells purified by repeated counter-flow elutriation, whereas no mRNA expression for UTP receptors P2Y(4) and P2Y(2) could be detected. Functional in vitro experiments revealed that the P2Y(6) agonist UDPbetaS dose-dependently enhanced insulin and glucagon release during short-term incubation (1h), while P2Y(6) activation during a longer period (24h), selectively increased insulin release, especially at high glucose levels. The corresponding EC(50) value for UDPbetaS ranged from 3.2x10(-8)M to 1.6x10(-8)M for both glucose concentrations. The P2Y(6) antagonist MRS2578 inhibited the effects of UDPbetaS, supporting a P2Y(6) specific effect. In addition to negative RT-PCR results, the lack of response to UTPgammaS a selective P2Y(2/4) agonist further rule out the involvement of P2Y(2/4) receptors in the islet hormone release. Our results suggest a modulatory role for UDP via a functional active P2Y(6) receptor in the regulation of islet hormone release. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Biochemical and Biophysical Research Communications
volume
6;370
issue
3
pages
499 - 503
publisher
Elsevier
external identifiers
  • wos:000255664700023
  • pmid:18387359
  • scopus:42749088832
ISSN
1090-2104
DOI
10.1016/j.bbrc.2008.03.119
language
English
LU publication?
yes
id
db4183b6-87e1-4c3d-b981-dc173c993b85 (old id 1147805)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/18387359?dopt=Abstract
date added to LUP
2008-05-06 15:03:14
date last changed
2017-10-22 05:01:51
@article{db4183b6-87e1-4c3d-b981-dc173c993b85,
  abstract     = {We examined the transcriptional expression and functional effects of receptors for the extracellular pyrimidines uridine triphosphate (UTP) and uridine diphosphate (UDP), on insulin and glucagon secretion in isolated mouse pancreatic islets and purified beta-cells. Using real-time PCR, the UDP receptor P2Y(6) was found to be highly expressed in both whole islets and beta-cells purified by repeated counter-flow elutriation, whereas no mRNA expression for UTP receptors P2Y(4) and P2Y(2) could be detected. Functional in vitro experiments revealed that the P2Y(6) agonist UDPbetaS dose-dependently enhanced insulin and glucagon release during short-term incubation (1h), while P2Y(6) activation during a longer period (24h), selectively increased insulin release, especially at high glucose levels. The corresponding EC(50) value for UDPbetaS ranged from 3.2x10(-8)M to 1.6x10(-8)M for both glucose concentrations. The P2Y(6) antagonist MRS2578 inhibited the effects of UDPbetaS, supporting a P2Y(6) specific effect. In addition to negative RT-PCR results, the lack of response to UTPgammaS a selective P2Y(2/4) agonist further rule out the involvement of P2Y(2/4) receptors in the islet hormone release. Our results suggest a modulatory role for UDP via a functional active P2Y(6) receptor in the regulation of islet hormone release.},
  author       = {Parandeh, Fariborz and Abaraviciene, Sandra Meidute and Amisten, Stefan and Erlinge, David and Salehi, S Albert},
  issn         = {1090-2104},
  language     = {eng},
  number       = {3},
  pages        = {499--503},
  publisher    = {Elsevier},
  series       = {Biochemical and Biophysical Research Communications},
  title        = {Uridine diphosphate (UDP) stimulates insulin secretion by activation of P2Y(6) receptors.},
  url          = {http://dx.doi.org/10.1016/j.bbrc.2008.03.119},
  volume       = {6;370},
  year         = {2008},
}