Uridine diphosphate (UDP) stimulates insulin secretion by activation of P2Y6 receptors

Biochem Biophys Res Commun. 2008 Jun 6;370(3):499-503. doi: 10.1016/j.bbrc.2008.03.119. Epub 2008 Apr 1.

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 3.2 x 10(-8)M to 1.6 x 10(-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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Female
  • Glucagon / metabolism
  • Insulin / metabolism*
  • Insulin Secretion
  • Insulin-Secreting Cells / drug effects
  • Insulin-Secreting Cells / metabolism*
  • Islets of Langerhans / drug effects
  • Islets of Langerhans / metabolism
  • Mice
  • Mice, Inbred Strains
  • Purinergic P2 Receptor Agonists*
  • Receptors, Purinergic P2 / genetics
  • Receptors, Purinergic P2 / metabolism
  • Uridine Diphosphate / analogs & derivatives
  • Uridine Diphosphate / metabolism*
  • Uridine Diphosphate / pharmacology

Substances

  • Insulin
  • Purinergic P2 Receptor Agonists
  • Receptors, Purinergic P2
  • purinoceptor P2Y6
  • uridine 5'-O-thiodiphosphate
  • Uridine Diphosphate
  • Glucagon