Autoimmune is a type 1 Diabetes

Type 1 diabetes (T1D) is an autoimmune disease caused by the selective destruction of insulin-producing β-cells. The trigger, however, remains unknown. Postnatal environmental determinants have been thoroughly studied as risk factors but a crucial phase for the immune system development, the late prenatal stage, has been poorly investigated. Specifically, the interaction of drugs commonly used during late pregnancy with T1D and the pancreatic β-cells remains unexplored. Nonetheless, some studies reveal the importance of the prenatal stage and the prematurity of the newborn in the development of T1D. An indirect demonstration of how critical the in utero environment is in T1D development arises from the studies in twins: heterozygotic twins have an increased concordance of T1D when compared to non-twin siblings, underlining the potential relevance of prenatal factors and their influence in the development of autoimmunity.

Synthetic glucocorticoids, most often betamethasone, are routinely given to mothers at risk of preterm birth between 24 and 34 weeks of gestation. A single course of prenatal betamethasone reduces the occurrence and severity of respiratory distress syndrome and improves the survival chances in premature infants. Another glucocorticoid used for lung maturation is dexamethasone and produces similar results on the new born survivability. These synthetic glucocorticoids cross the placenta and accelerate foetal lung maturation, achieving maximum benefit between 24 h and 7 days after administration. Betamethasone is a poor substrate for the glucocorticoid inactivating enzyme 11beta-hydroxysteroid-dehydrogenase 2 (11βHSD2), therefore, its bioactivity in the foetus lasts for several days and it is known to exert long-lasting effects on the hypothalamic-pituitary-adrenal (HPA) axis and cognition in children.

Glucocorticoids exert their effects by binding nuclear receptors that are ligand-dependent transcription factors. They can regulate gene transcription, either by direct binding to DNA or by interacting with other transcription factors. Glucocorticoid receptors (GR) are ubiquitously expressed; however, due to the variation in the genomic location of GR binding, the transcriptional responses to glucocorticoids are cell type-specific. Moreover, polymorphisms of the GR result in alterations in their responsiveness to glucocorticoids and in gene expression. In addition, human GR receptor can be a target of endocrine disruptors such as pesticides that, in combination with antenatal glucocorticoids, could increase developmental neurotoxicity.

Regards,

John
Editorial Assistant
Pancreatic Disorder and Therapy