Perinatal programming of the endocrine pancreas by maternal diabetes: impact on the development of the β-cell mass and glucose homeostasis in the offspring

In recent years, epidemiological findings had strongly suggested that in utero exposure to maternal diabetes is associated with abnormal insulin secretion and glucose homeostasis in the offspring and may participate in the excess of maternal transmission in type 2 diabetes (T2D). From human studies, isolation of the respective contribution of genetic v. perinatal environmental factors is hardly attainable. The Goto-Kakizaki (GK) rat is a spontaneous model of T2D with decreased β-cell mass observed as early as in fetal life, followed by altered β-cell function during postnatal life. This model is a useful tool to investigate whether the deficit of pancreatic β-cell number is determined genetically, environmentally or both. The aim of our work was to determine the contribution of the maternal hypergly-cemia on the development of β-cell mass and function in a normal Wistar conceptus (in the absence of diabetes predisposing genes). Using an embryo transfer technology, we implated fertilized Wistar oocytes into pseudo-pregnantdiabetic GK females.b-cell mass, cell proliferation and cell neogenesis were measured in the pancreas of E18.5 fetuses. The pups were either suckled by their GK mothers or cross-fostered to non-diabetic Wistar dams to evaluate the proper influence of perinatal nutritional environment.β-cell mass, basal glycemia and glucose tolerance were measured in 8–10 weeks old offspring. We showed that maternal diabetes impairs early development of the β-cell mass in Wistar offspring. This defect is maintained in the pancreas of adult offspring reared either by Wistar or by diabetic GK dams. In this group, the glucose tolerance was also altered in the adult offspring. Taken together, our data provide evidence for a deleterious impact of maternal hyperglycemiao on b-cell development and growth in Wistaroffspring at no spontaneous risk of diabetes. These data contribute to the better understanding of the effects of exposure to maternal diabetic environment and could bear important public health implications in the present context of growing diabetes epidemic.