Author/Editor		Ma, Wenzhen; Chen, Xingjuan; Černe, Rok; Syed, Samreen K.; Ficorilli, James V.; Cabrera, Over; Obukhov, Alexander G.; Efanov, Alexander M.
Title		Catechol estrogens stimulate insulin secretion in pancreatic [beta]-cells via activation of the transient receptor potential A1(TRPA1) channel
Type		članek
Vol. and No.		Letnik 294, št. 8
Publication year		2019
Volume		str. 2935-2946
ISSN		0021-9258 - The Journal of biological chemistry
Language		eng
Abstract		Estrogen hormones play an important role in controlling glucose homeostasis and pancreatic [beta]-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 [beta]-cell function. In this study, we evaluated the effects of major natural estrogen metabolites, catechol estrogens, on insulin secretion in pancreatic [beta]-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.
Keywords		estrogen ion channel insulin secretion estrogen ionski kanal izločanje insulina