Endocrine Abstracts

Background: Pregnancy induces pancreatic islet β-cell mass expansion, but the exact mechanisms responsible remain unclear. It is nevertheless believed that disturbances in the process contribute to the development of gestational diabetes. The current study investigates the impact of pregnancy and cafeteria diet on islet morphology, cellular proliferation/apoptosis as well as endocrine cell lineage plasticity.

Methods: Non-pregnant and pregnant Ins1^Cre/+;Rosa26-eYFP transgenic mice with fluorescently tagged beta cells were maintained on either normal rodent breeding diet or cafeteria diet comprising brie cheese, peanuts, peanut butter, Nutella and chocolate with 30% sucrose water. Pancreatic tissue was obtained at 18 days gestation and immunohistochemical changes in islet morphology were assessed.

Results: Normal diet Ins1^Cre/+;Rosa26-eYFP pregnant mice displayed increased (P < 0.01) body-weight and slightly elevated (P < 0.05) blood glucose. Cafeteria feeding attenuated this weight gain, whilst causing further increases (P < 0.01) in glucose. Pregnant Ins1^Cre/+;Rosa26-eYFP mice exhibited typical 1.5-2.0-fold expansion in islet area and β-cell area. These changes were related to increased β-cell proliferation and survival (0.2-3.0-fold, P < 0.001) as well as enhanced α and ductal β-cell transdifferentiation (1.3-3.0-fold, P < 0.01-0.001), alongside a 6.0-fold increase (P < 0.001) in β-cell neogenesis. In contrast, pregnancy-induced islet adaptations were severely compromised by consumption of a cafeteria diet, with no significant expansion of islet or β-cell area. Moreover, high levels of β-cell apoptosis (0.2-3.0-fold, P < 0.001) and reduced proliferation (0.8-1.2-fold, P < 0.05), together with increased β-cell dedifferentiation (1.5-3.0-fold, P < 0.001) and a lack of β-cell neogenesis adaptations, were observed in pregnant mice maintained on a cafeteria diet.

Conclusion: Augmentation of β-cell mass during gestation arises through various mechanisms that include proliferation and survival of existing β-cells, transdifferentiation of α and ductal cells as well as β-cell neogenesis. Remarkably, cafeteria feeding almost entirely annuls these pregnancy-induced islet adaptations, which may contribute to the development of gestational diabetes in the setting of dietary-induced metabolic stress.