Abstracts

#44 Gestational Diabetes Mellitus (GDM) Exposure and Postnatal Diet Influence Pancreatic Islet Function of the Rat Offspring


Taylor S Morriseau, University of Manitoba; Navdeep Brar, University of Manitoba; Prasoon Agarwal, University of Manitoba; Mario A Fonseca, University of Manitoba; Stephanie M Kereliuk, University of Manitoba; Laura K Cole, University of Manitoba; Bo Xiang, University of Manitoba; Nivedita Seshadri, University of Manitoba; Kristin L Hunt, University of Manitoba; Grant M Hatch, University of Manitoba; Christine A Doucette, University of Manitoba; Vernon W Dolinsky, University of Manitoba


Introduction

As rates of obesity surge to epidemic proportions, GDM has emerged as the most common complication of pregnancy. GDM exposure and obesity are strong risk factors for type 2 diabetes development; however, connections between GDM exposure, postnatal diet, and pancreatic islet dysfunction in offspring metabolic health remain unclear. We hypothesize that GDM exposure drives changes in islet gene expression and impairs islet structure and function, which is worsened by a postnatal high-fat and sucrose (HFS) diet.


Methods

GDM was induced in female rats using a HFS (45% kcal% fat) diet. Litters of LEAN or GDM dams were divided and pups were weaned onto a low-fat (LF; 10% kcal% fat) or HFS diet for 12 weeks. Pancreata and islets were isolated from 15-week-old offspring to analyze pancreas morphometry, gene expression (RNA-seq), and glucose-stimulated insulin secretion.


Results

GDM exposure induced a 1.3-fold reduction in glucose-stimulated insulin secretion (GSIS), which was exacerbated by a postnatal HFS exposure (4.3-fold reduction). Offspring of LEAN dams fed a postnatal HFS diet showed increased islet numbers (1.6-fold) and mean islet area (1.8-fold), and GDM exposure attenuated these adaptive responses. Islets from GDM-exposed and LF-fed offspring revealed a 2-fold upregulation in 37 genes (including T2D-associated genes Il-6 and Angptl4) and 3 downregulated genes. In the GDM-exposed and HFS-diet group, a unique set of 35 genes were upregulated and 135 genes were downregulated.


Conclusion

GDM exposure impaired the adaptive increase in the number and size of offspring’s islets in response to a HFS diet, concomitant with a further reduction in glucose-stimulated insulin secretion. GDM-induced alterations in gene expression cumulatively interact with the postnatal HFS diet to worsen metabolic health outcomes in the offspring.