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- Soriano, S (author)
Rapid regulation of K(ATP) channel activity by 17{beta}-estradiol in pancreatic {beta}-cells involves the estrogen receptor {beta} and the atrial natriuretic peptide receptor
- Article/chapterEnglish2009
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- The Endocrine Society,2009
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- LIBRIS-ID:oai:prod.swepub.kib.ki.se:119683066
- http://kipublications.ki.se/Default.aspx?queryparsed=id:119683066URI
- https://doi.org/10.1210/me.2009-0287DOI
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- Language:English
- Summary in:English
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- 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 [Ca2+]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 the membrane guanylate 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.
Added entries (persons, corporate bodies, meetings, titles ...)
- Ropero, AB (author)
- Alonso-Magdalena, P (author)
- Ripoll, C (author)
- Quesada, I (author)
- Gassner, B (author)
- Kuhn, M (author)
- Gustafsson, JAKarolinska Institutet (author)
- Nadal, A (author)
- Karolinska Institutet (creator_code:org_t)
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- In:Molecular endocrinology (Baltimore, Md.): The Endocrine Society23:12, s. 1973-19821944-99170888-8809
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