Pancreatic islet adaptation in pregnancy and postpartum.

Pancreatic islets, particularly insulin-producing ß-cells, are central regulators of glucose homeostasis capable of responding to a variety of metabolic stressors. Pregnancy is a unique physiological stressor, necessitating the islets to adapt to the complex interplay of maternal and fetal-placental factors influencing the metabolic milieu. In this review we highlight studies defining gestational adaptation mechanisms within maternal islets and emerging studies revealing islet adaptations during the early postpartum and lactation periods. These include adaptations in both ß and in 'non-ß' islet cells. We also discuss insights into how gestational and postpartum adaptation may inform pregnancy-specific and general mechanisms of islet responses to metabolic stress and contribute to investigation of gestational diabetes.

Role of Delta/Notch-like EGF-related receptor in blood glucose homeostasis.

Cell-cell interactions are necessary for optimal endocrine functions in the pancreas. ß-cells, characterized by the expression and secretion of the hormone insulin, are a major constituent of functional micro-organs in the pancreas known as islets of Langerhans. Cell-cell contacts between ß-cells are required to regulate insulin production and glucose-stimulated insulin secretion, which are key determinants of blood glucose homeostasis. Contact-dependent interactions between ß-cells are mediated by gap junctions and cell adhesion molecules such as E-cadherin and N-CAM. Recent genome-wide studies have implicated Delta/Notch-like EGF-related receptor (Dner) as a potential susceptibility locus for Type 2 Diabetes in humans. DNER is a transmembrane protein and a proposed Notch ligand. DNER has been implicated in neuron-glia development and cell-cell interactions. Studies herein demonstrate that DNER is expressed in ß-cells with an onset during early postnatal life and sustained throughout adulthood in mice. DNER loss in adult ß-cells in mice (ß-Dner cKO mice) disrupted islet architecture and decreased the expression of N-CAM and E-cadherin. ß-Dner cKO mice also exhibited impaired glucose tolerance, defects in glucose- and KCl-induced insulin secretion, and decreased insulin sensitivity. Together, these studies suggest that DNER plays a crucial role in mediating islet cell-cell interactions and glucose homeostasis.

Tamoxifen Improves Glucose Tolerance in a Delivery-, Sex-, and Strain-Dependent Manner in Mice.

Tamoxifen, a selective estrogen-receptor modulator, is widely used in mouse models to temporally control gene expression but is also known to affect body composition. We report that tamoxifen has significant and sustained effects on glucose tolerance, independent of effects on insulin sensitivity, in mice. IP, but not oral, tamoxifen delivery improved glucose tolerance in three inbred mouse strains. The extent and persistence of tamoxifen-induced effects were sex and strain dependent. These findings highlight the need to revise commonly used tamoxifen-based protocols for gene manipulation in mice by including longer chase periods after injection, oral delivery, and the use of tamoxifen-treated littermate controls.