Objective: 

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.

Methods: 

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

Results: 

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.

Conclusions: 

We conclude that ER b agonists should be considered as new antidiabetic drugs.