Catechol estrogens stimulate insulin secretion in pancreatic β-cells via activation of the transient receptor potential A1 (TRPA1) channel

Wenzhen Ma, Xingjuan Chen, Rok Cerne, Samreen K. Syed, James V. Ficorilli, Over Cabrera, Alexander Obukhov, Alexander M. Efanov

Research output: Contribution to journalArticle

Abstract

Estrogen hormones play an important role in controlling glucose homeostasis and pancreatic β-cell function. Despite the significance of estrogen hormones for regulation of glucose metabolism, little is known about the roles of endogenous estrogen metabolites in modulating pancreatic β-cell function. In this study, we evaluated the effects of major natural estrogen metabolites, catechol estrogens, on insulin secretion in pancreatic β-cells. We show that catechol estrogens, hydroxylated at positions C2 and C4 of the steroid A ring, rapidly potentiated glucose-induced insulin secretion via a nongenomic mechanism. 2-Hydroxyestrone, the most abundant endogenous estrogen metabolite, was more efficacious in stimulating insulin secretion than any other tested catechol estrogens. In insulin-secreting cells, catechol estrogens produced rapid activation of calcium influx and elevation in cytosolic free calcium. Catechol estrogens also generated sustained elevations in cytosolic free calcium and evoked inward ion current in HEK293 cells expressing the transient receptor potential A1 (TRPA1) cation channel. Calcium influx and insulin secretion stimulated by estrogen metabolites were dependent on the TRPA1 activity and inhibited with the channel-specific pharmacological antagonists or the siRNA. Our results suggest the role of estrogen metabolism in a direct regulation of TRPA1 activity with potential implications for metabolic diseases.

Original languageEnglish (US)
Pages (from-to)2935-2946
Number of pages12
JournalThe Journal of biological chemistry
Volume294
Issue number8
DOIs
StatePublished - Feb 22 2019

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Catechol Estrogens
Transient Receptor Potential Channels
Estrogens
Chemical activation
Insulin
Metabolites
Calcium
Metabolism
Glucose
Hormones
HEK293 Cells
Metabolic Diseases
Insulin-Secreting Cells
Small Interfering RNA
Cations
Homeostasis
Steroids
Cells
Pharmacology
Ions

Keywords

  • estrogen; ion channel; transient receptor potential channels (TRP channels); insulin secretion; pancreatic islet

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Catechol estrogens stimulate insulin secretion in pancreatic β-cells via activation of the transient receptor potential A1 (TRPA1) channel. / Ma, Wenzhen; Chen, Xingjuan; Cerne, Rok; Syed, Samreen K.; Ficorilli, James V.; Cabrera, Over; Obukhov, Alexander; Efanov, Alexander M.

In: The Journal of biological chemistry, Vol. 294, No. 8, 22.02.2019, p. 2935-2946.

Research output: Contribution to journalArticle

Ma, Wenzhen ; Chen, Xingjuan ; Cerne, Rok ; Syed, Samreen K. ; Ficorilli, James V. ; Cabrera, Over ; Obukhov, Alexander ; Efanov, Alexander M. / Catechol estrogens stimulate insulin secretion in pancreatic β-cells via activation of the transient receptor potential A1 (TRPA1) channel. In: The Journal of biological chemistry. 2019 ; Vol. 294, No. 8. pp. 2935-2946.
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