The estrogen receptors ERalpha and ERbeta are currently considered important molecules in glucose and lipid metabolism, although their specific roles in pancreatic beta-cells are still greatly unknown. The function of pancreatic beta-cells is the biosynthesis and release of insulin, the only hormone able to decrease blood glucose levels. It has been recently described that ERalpha plays an essential role in the regulation of insulin biosynthesis by 17beta-estradiol, contributing to an enhancement of glucose-induced insulin secretion (Alonso-Magdalena et al, 2008). In addition, 17beta-estradiol rapidly (in minutes) decreases KATP channel activity and increases insulin release in a cGMP dependent manner (Nadal et al, 1998; Ropero et al, 1999). The 17beta-estradiol-induced reduction of KATP channel activity is mimicked by the ERbeta agonist, DPN; this action is missing in beta-cells from ERbeta knock-out mice (BERKO). Both the blockade of KATP channels and the release of insulin are abolished in beta-cells obtained for guanylyl cyclase A knock out mice (GC-A KO). Therefore, evidence indicate that the estrogen receptor ERbeta and the guanylyl cyclase-A receptor (GC-A) are involved in the 17beta-estradiol triggered action in beta-cells. These results may be relevant to clarify the role of estrogen receptors in the endocrine pancreas adaptation to pregnancy and point to ERbeta agonists as effective insulinotropic agents.
University College Dublin (2009) Proc Physiol Soc 15, SA22
Research Symposium: Novel ERα and ERβ mediated actions in mouse pancreatic β-cells
S. Soriano1, A. B. Ropero1, P. Alonso-Magdalena1, C. Ripoll1, I. Quesada1, B. Gassner2, M. Kuhn2, J. Gustafsson3,4, A. Nadal1
1. Instituto de Bioingeniería and CIBERDEM, Universidad Miguel Hernandez de Elche, Elche, Alicante, Spain. 2. Institute of Physiology, University of Würzburg, Würzburg, Germany. 3. Center for Nuclear Receptors and Cell Signaling, University of Houston, Houston, Texas, USA. 4. Department of Biosciences and Nutrition, Karolinska Institute, Huddinge, Sweden.
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