Cafeteria diet compromises natural adaptations of islet cell transdifferentiation and turnover in pregnancy.

backgroundPancreatic islet β-cell mass expands during pregnancy, but underlying mechanisms are not fully understood. This study examines the impact of pregnancy and cafeteria diet on islet morphology, associated cellular proliferation/apoptosis rates as well as β-cell lineage.

methodsNon-pregnant and pregnant Ins1

resultsPregnant normal diet mice displayed an increase in body weight and glycaemia. Cafeteria feeding attenuated this weight gain while causing overt hyperglycaemia. Pregnant mice maintained on a normal diet exhibited typical expansion in islet and β-cell area, owing to increased β-cell proliferation and survival as well as ductal to β-cell transdifferentiation and β-cell neogenesis, alongside decreased β-cell dedifferentiation. Such pregnancy-induced islet adaptations were severely restricted by cafeteria diet. Accordingly, islets from these mice displayed high levels of β-cell apoptosis and dedifferentiation, together with diminished β-cell proliferation and lack of pregnancy-induced β-cell neogenesis and transdifferentiation, entirely opposing islet cell modifications observed in pregnant mice maintained on a normal diet.

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