In vivo models of gestational and type 2 diabetes mellitus characterized by endocrine pancreas cell impairments

Abstract

Insulin resistance contributes to the development of various diseases, including type 2 diabetes and gestational diabetes. Even though gestational diabetes is specific to pregnancy, it can result in long-term glucose intolerance and type 2 diabetes after delivery. Given the substantial health and economic burdens associated with diabetes, it is imperative to better understand the mechanisms leading to insulin resistance and type 2 diabetes so that treatments targeted at reversing symptoms can be developed. Considering that the endocrine cells of the pancreas (islets of Langerhans) largely contribute to the pathogenesis of diabetes (beta-cell insufficiency and dysfunction), the elucidation of the various mechanisms of endocrine cell plasticity is important to understand. By better defining these mechanisms, targeted therapeutics can be developed to reverse symptoms of beta-cell deficiency and insulin resistance in diabetes. Animal models play an important role in better understanding these mechanisms, as techniques for in vivo imaging of endocrine cells in the pancreas are limited. Therefore, this review article will discuss the available rodent models of gestational and type 2 diabetes that are characterized by endocrine cell impairments in the pancreas, discuss the models with a comparison to human diabetes, and explore the potential mechanisms of endocrine cell plasticity that contribute to these phenotypes, as these mechanisms could ultimately be used to reverse blood glucose dysregulation in diabetes.