Gestational Diabetes Adversely Affects Pancreatic Islet Architecture and Function in the Male Rat Offspring

Authors:
Publisher website
Google Scholar
Abstract
Fetal exposure to gestational diabetes mellitus (GDM) and poor postnatal diet are strong risk factors for type 2 diabetes development later in life, but the mechanisms connecting GDM exposure to offspring metabolic health remains unclear. In this study, we aim to determine how GDM interacts with the postnatal diet to affect islet function in the offspring as well as characterize the gene expression changes in the islets. GDM was induced in female rats using a high fat and sucrose (HFS) diet and litters from Lean or GDM dams were weaned on to a low-fat (LF) or HFS diet. Compared to the lean control offspring, GDM exposure reduced glucose-stimulated insulin secretion in islets isolated from 15 week-old offspring, which was additively worsened when GDM exposure was combined with postnatal HFS diet consumption. In the HFS-fed offspring of Lean dams, islet size and number increased, an adaptation that was not observed in the HFS-fed offspring of GDM dams. Islet gene expression in the offspring of GDM dams was altered in such categories as inflammation (e.g. Il1b, Ccl2), mitochondrial function/oxidative stress resistance (e.g. Atp5f1, Sod2) and ribosomal proteins (e.g. Rps6, Rps14). These results demonstrate that GDM exposure induced marked changes in gene expression in the male young adult rat offspring that cumulatively interact to worsen islet function, whole-body glucose homeostasis and adaptations to HFS diets.
Funding Information
  • Canadian Institutes of Health Research (144626, 136885)
  • Research Manitoba

This publication has 33 references indexed in Scilit: