Gestational diabetes adversely affects pancreatic islet development and function in the rat offspring

Gestational diabetes mellitus (GDM) exposure and obesity are strong risk factors for type 2 diabetes development; however, the connections between GDM exposure, postnatal diet and islet dysfunction in offspring metabolic health remain unclear. Reduced glucose-stimulated insulin secretion was observed in islets isolated from 15-week-old offspring prenatally exposed to GDM, which was exacerbated by postnatal HFS 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. Islets from GDM exposed offspring revealed upregulation of 102 genes (e.g. Sod2, Il1b) and 13 downregulated genes. In the GDM offspring that consumed a postnatal HFS-diet, 126 genes were significantly upregulated (e.g. Ccl2, Rps14, Atp5f1) and 17 genes were downregulated (e.g. Hnf1a, Slc2a2). These results demonstrate that GDM exposure induced changes in gene expression in the young adult rat offspring that worsen islet function and whole-body glucose homeostasis. GDM was induced in female Sprague-Dawley rats using a high fat and sucrose (HFS) diet and litters from Lean (low-fat or LF) fed dams or the GDM (HFS-fed) dams. Pups were weaned on to a LF or HFS diets for 12 weeks. Islets and pancreata were isolated to analyze endocrine pancreas morphology, gene expression (RNA-seq) and hormone contents.