Acta Physiologica 2011; Volume 203, Supplement 686
Joint Congress of FEPS and Turkish Society of Physiological Sciences
ROLE OF ESTROGEN RECEPTOR BETA IN PANCREATIC BETA-CELL FUNCTION
Abstract number: OC01
Magdalena1 Paloma Alonso, Soriano1 Sergi, Arevalo1 Marta García, Quesada1 Ivan, Fuentes1 Esther, Gustafsson2 Jan Ake, Nadal1 Angel
1CIBER of Diabetes and Associated Metabolic Diseases, CIBERDEM and Institute of Bioengineering, University Miguel Hernandez of Elche, Elche, Spain
2Department of Cell Biology and Biochemistry, Center fo Nuclear Receptors and Cell Signaling, University of Houston, SA
Type 2 diabetes is characterized by the emergence of fasting hyperglycemia. This hyperglycemia is associated with an inadequate insulin secretion from pancreatic b-cells to compensate for insulin-resistance in peripheral tissues. The ATP-potassium channel (KATP channel) is the key molecule involved in glucose-stimulated insulin secretion (GSIS). We have previously demonstrated that physiological concentrations of 17b-estradiol (E2) decrease KATP channel activity thus enhancing insulin secretion. Here we evaluate the new role of estrogen receptor beta (ER b) as an insulinotropic molecule.
C57BL/6 and ER b -/- mice were used. Electrical activity and calcium records were analyzed in the whole islet of Langerhans. Plasma insulin, leptin, tryglicerides and glycerol levels were measured by ELISA
In vitro studies demonstrate that low doses of WAY 200070, an ER b specific agonist, decrease KATP channel activity and enhance GSIS in the presence of stimulatory (7 and 16 mM glucose) but not low glucose concentrations. In a set of in vivo experiments we showed that a single-administration of WAY 200070 leads to an improvement in the plasma glucose response to a glucose challenge with a concomitant increase in insulin levels. Thus, we next studied the potential clinical use of ERb agonists by using streptozotocin-nicotinamide-induced mildly diabetic mice. These animals exhibit moderate hyperglycaemia and impaired glucose tolerance because of the loss of early-phase insulin secretion. One-week treatment with the ER b agonist caused a significant improvement in glucose tolerance, with a significant increase in the plasma insulin and a decrease of glycerol levels in the diabetic treated group.
We conclude that ER b agonists should be considered as new antidiabetic drugs.
To cite this abstract, please use the following information:
Acta Physiologica 2011; Volume 203, Supplement 686 :OC01