Maternal vitamin D-restricted diet has consequences in the formation of pancreatic islet/insulin-signaling in the adult offspring of mice.

Abstract

The maternal deficiency of vitamin D can act on organogenesis in mice offspring, being a risk factor for chronic diseases in adulthood. This study investigates the effects of maternal deficiency of vitamin D on structural islet remodeling and insulin-signaling pathway in the offspring. We studied male C57Bl/6 offspring at 3-month old (n=10/group) from mother fed one of the two diets: control diet (C) or vitamin D-restricted diet (VitD-). After weaning, offspring only fed the control diet ad libitum. In the offspring, we studied insulin production, islet remodeling, and islet protein expression of the insulin-signaling pathway (Western blotting, isolated islet, n=5/group). VitD- offspring showed greater glycemia (P=0.012), smaller beta-cell mass (P=0.014), and hypoinsulinemia (P=0.024) than C offspring. Comparing VitD- offspring with C offspring, we observed lower protein levels in islet of insulin (P=0.003), insulin receptor substrate-1 (P=0.025), phosphatidylinositol-3-kinases (P=0.045), 3-phosphoinositide-dependent protein kinase 1 (P=0.017), protein kinase B (P=0.028), with reduced expression of pancreas/duodenum homeobox-1 (PDX-1) (P=0.016), glucose transporter-2 (P=0.003), and glucokinase (P=0.045). The maternal vitamin D-restricted diet modifies the development of the pancreas of the offspring, leading to islet remodeling and altered insulin-signaling pathway. The decrease of PDX-1 is probably significant to the changes in the beta-cell mass and insulin secretion in adulthood.