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

Endocrine. 2016 Oct;54(1):60-69. doi: 10.1007/s12020-016-0973-y. Epub 2016 May 3.

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.

Keywords: Fetal programming; FoxO1; Insulin pathway; PDX-1; Pancreas.

MeSH terms

  • Animals
  • Blood Glucose / metabolism
  • Diet*
  • Female
  • Insulin / metabolism*
  • Islets of Langerhans / metabolism*
  • Maternal Nutritional Physiological Phenomena / physiology*
  • Mice
  • Pregnancy
  • Prenatal Exposure Delayed Effects / metabolism*
  • Signal Transduction
  • Vitamin D / metabolism
  • Vitamin D Deficiency / metabolism*

Substances

  • Blood Glucose
  • Insulin
  • Vitamin D