This review focuses on different animal models of nutrient perturbations, inclusive of restrictive and excessive states mimicking human situations during pregnancy and lactation that cause aberrations in the offspring. These aberrations consist of diminished
insulin sensitivity in the presence of defective
insulin production. These phenotypic changes are due to altered peripheral tissue post-
insulin receptor signaling mechanisms and pancreatic beta-islet
insulin synthesis and secretion defects. While these changes during in utero or postnatal life serve as essential adaptations to overcome adverse conditions, they become maladaptive subsequently and set the stage for
type 2 diabetes mellitus. Pregnancy leads to
gestational diabetes with trans-generational propagation of the
insulin resistant phenotype. This is in response to the metabolically aberrant maternal in utero environment, and tissue specific epigenetic perturbations that permanently alter expression of critical genes transmitted to future generations. These heritable aberrations consisting of altered DNA methylation and histone modifications remodel
chromatin and affect transcription of key genes. Along with an altered in utero environment, these
chromatin modifications contribute to the world-wide epidemic of
type 2 diabetes mellitus, with nutrient excess dominating in developed and nutrient restriction in developing countries.