Rapid regulation of KATP channel activity by 17β-estradiol in pancreatic β-cells involves the estrogen receptor β and the atrial natriuretic peptide receptor

Sergi Soriano, Ana B. Ropero, Paloma Alonso-Magdalena, Cristina Ripoll, Ivan Quesada, Birgit Gassner, Michaela Kuhn, Jan Åke Gustafsson, Angel Nadal

Research output: Contribution to journalArticle

70 Scopus citations

Abstract

The ATP-sensitive potassium (KATP) channel is a key molecule involved in glucose-stimulated insulin secretion. The activity of this channel regulates β-cell membrane potential, glucose- induced [Ca 2+]i signals, and insulin release. In this study, the rapid effect of physiological concentrations of 17β-estradiol (E2) on KATP channel activity was studied in intact β-cells by use of the patch-clamp technique. When cells from wild-type (WT) mice were used, 1 nM E2 rapidly reduced KATP channel activity by 60%. The action of E2 on KATP channel was not modified in β-cells from ERα-/-mice, yet it was significantly reduced in cells from ERβ-/- mice. The effect of E2 was mimicked by the ERβ agonist 2,3-bis(4-hydroxyphenyl)-propionitrile (DPN). Activation of ERβ by DPN enhanced glucose-induced Ca2+ signals and insulin release. Previous evidence indicated that the acute inhibitory effects of E2 on KATP channel activity involve cyclic GMP and cyclic GMP-dependent protein kinase. In this study,we used β-cells from mice with genetic ablation of themembraneguanylate cyclase A receptor for atrial natriuretic peptide (also called the atrial natriuretic peptide receptor) (GC-A KO mice) to demonstrate the involvement of this membrane receptor in the rapid E2 actions triggered in β-cells. E2 rapidly inhibited KATP channel activity and enhanced insulin release in islets from WT mice but not in islets from GC-A KO mice. In addition, DPN reduced KATP channel activity in β-cells from WT mice, but not in β-cells from GC-A KO mice. This work unveils a new role for ERβ as an insulinotropic molecule that may have important physiological and pharmacological implications.

Original languageEnglish (US)
Pages (from-to)1973-1982
Number of pages10
JournalMolecular Endocrinology
Volume23
Issue number12
DOIs
StatePublished - Dec 2009

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology

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