Preconception alcohol exposure increases the susceptibility to diabetes in the offspring

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.