Preconception alcohol exposure increases the susceptibility to diabetes in the offspring
Al-Yasari, Ali et al. (2020), Preconception alcohol exposure increases the susceptibility to diabetes in the offspring, Dryad, Dataset, https://doi.org/10.5061/dryad.brv15dv7x
Preconception alcohol exposure in mothers has recently been shown to increase stress responses and anxiety behaviors in their offspring during the adult period. One hypothesis is that alcohol-induced genetic modifications in germ cells of the mother could have been transmitted to the offspring to manifest the endophenotypes. In this study, transcriptome analysis of germ cells of female rats given binge-like alcohol identified altered stress gene regulation networks involving glucose metabolism and diabetes mellitus. Endocrine tests involving oral glucose tolerance, glucose-stimulated insulin secretion, and insulin tolerance in the male and female offspring of mothers given binge-like alcohol during the preconception period showed significant hyperglycemia and hypoinsulinemia. These offspring also showed increased levels of inflammatory cytokines and cellular apoptosis in the pancreas and altered insulin production and action on glucose metabolism, particularly insulin signaling molecules, in the liver. These animals, when subjected to a high-fat diet and streptozotocin injection for induction of type 2 diabetes, showed a higher response than control offspring. Preconception alcohol exposed offspring also showed reduced number of stress and glucose regulatory proopiomelanocortin (POMC) producing neurons in the hypothalamus, Replenishment of POMC neurons in the hypothalamus of these animals normalized glucose homeostasis and reduced the susceptibility to diabetes. These data suggest that preconception alcohol exposures alter glucose homeostasis and increase the susceptibility to diabetes by inducing POMC neuronal functional abnormalities, increasing pancreatic inflammation, and consequently lowering insulin production and action.