The endocrine pancreas is not considered a classic oestrogen target, although the effects of 17β-oestradiol in some physiological aspects of the islet of Langerhans have been known for a long time (Sutter-Dub, 2002). On the one hand, the level of plasma insulin is increased in pregnant rats in response to increased levels of sex steroids. Moreover, 17β-oestradiol at concentrations comparable to that of pregnancy enhances insulin secretion in perfused rat pancreas. On the other hand, in glucagon-releasing α-cells it was described that 17β-oestradiol produces an inhibitory effect on glucagon secretion. In spite of this evidence, the mechanism of action employed by 17β-oestradiol upon α and β cells is still largely unknown.

Recently, we have described a non-classical membrane oestrogen receptor (ncmER) in pancreatic β-cells (Nadal et al. 2000). It is responsible for a rapid insulinotropic effect of 17β-oestradiol when applied at physiological concentrations. Once bound to its membrane receptor, oestrogen triggers the synthesis of cGMP, which in turn activates protein kinase G. Then the ATP-dependent potassium channels (K_ATP) close in a PKG-dependent manner, causing the plasma membrane to depolarize, enhancing [Ca²⁺]_i (intracellular calcium) signals (Ropero et al. 1999). As a result, insulin secretion is increased and the transcription factor CREB is activated (Quesada et al. 2002). This receptor not only exists in pancreatic β-cells, but in α-cells as well (Ropero et al. 2002). When 17β-oestradiol acts through this receptor in α-cells, it inhibits low-glucose-induced [Ca²⁺]_i oscillations and therefore will abolish glucagon release.

This work was supported by grants from European Union-Comisión Interministerial de Ciencia y Tecnologia, Fundación Navarro-Trípodi and Instituto de Salud Carlos III-FISss.