Cited by 18Gestational Diabetes Research and ManagementBirth, Development, and HealthImmune Response and Inflammation

In utero exposure to gestational diabetes mellitus conditions TLR4 and TLR2 activated IL-1beta responses in spleen cells from rat offspring

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Li, Qian, Pereira, Troy J., Moyce, Brittany L., Mahood, Thomas H., Doucette, Christine A., Rempel, Julia, Dolinsky, Vernon W.·2016·Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease

Abstract

Fetal exposure to gestational diabetes mellitus (GDM) is associated with a higher risk of youth-onset insulin resistance and type 2 diabetes. We have previously shown that the rat offspring of GDM dams are insulin resistant when compared to the offspring of lean dams. Since inflammation influences insulin sensitivity, we examined the impact of fetal exposure to GDM on inflammatory responses in the offspring. In rats, we compared inflammatory activity in newborn pups as well as 16week-old young-adult offspring from lean control dams with offspring from high fat and sucrose diet (HFS)-induced GDM dams. To determine whether there are additive effects of exposure to GDM and post-weaning diets, offspring of lean and GDM dams were fed either low fat or HFS diets until 16weeks of age. Plasma levels of interleukin(IL)-1β were elevated in the offspring of GDM dams. To determine whether this was related to immune reactivity, spleen cells from both the newborn and 16week-old offspring were isolated and reactivity to the toll-like receptor activators, pam3CSK4 and lipopolysaccharides were measured over a 72h timeframe. Spleen cells of GDM dams exhibited sustained stimulation of interleukin(IL)-1β and IL-10 production, whereas IL-1β and IL-10 synthesis diminished over time in spleen cells from the offspring of lean dams. Additive effects of GDM exposure and post-weaning HFS diet were not observed, suggesting the effects of GDM on cytokine production are independent of the post-weaning diet. Thus, we conclude that exposure to GDM in utero may condition the immune reactivity of spleen cells.

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  1. D. Agarwal, R.B. Dange, J. Vila, A.J. Otamendi, J. Francis, Detraining differentially pre- served beneficial effects of exercise on hypertension: effects on blood pressure, car- diac function, brain inflammatory cytokines and oxidative stress, PLoS One 7 (2012), e52569.
  2. S. Hawkesworth, S.E. Moore, A.J. Fulford, G.R. Barclay, A.A. Darboe, H. Mark, O.A. Nyan, A.M. Prentice, Evidence for metabolic endotoxemia in obese and diabetic Gambian women, Nutr. Diabetes 3 (2013), e83.

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Authors
Li, Q., Pereira, T. J., Moyce, B. L., Mahood, T. H., Doucette, C. A., Rempel, J., & Dolinsky, V. W.
Affiliations
  • University of Manitoba (CA)
  • Children's Hospital Research Institute of Manitoba (CA)
Corresponding author
Dolinsky, Vernon W.
Venue
Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease
Publisher
Elsevier BV
Published
2016-11
Volume
1862
Issue
11
Pages
2137-2146
ISSN
0925-4439 (ISSN-L)
OpenAlex
W2508796801
Cited by
18
References
5
Citations by year
2025: 4 · 2024: 2 · 2023: 3 · 2022: 2 · 2021: 1 · 2020: 1 · 2019: 1 · 2018: 1 · 2017: 3
FWCI
2.15
Type
journal article
Language
en
Open access
Locations
  • Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Children's Hospital Research Institute of Manitoba (OG 2012-04)
  • Canadian Institutes of Health Research (MOP-136885)
Topics
  • Health Sciences › Medicine › Obstetrics and Gynecology › Gestational Diabetes Research and Management
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
  • Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
Keywords
gestational diabetes mellitus, prenatal exposure, offspring, type 2 diabetes risk, insulin resistance, inflammation, IL-1β, IL-10, TLR4, TLR2, splenocytes, immunoreactivity, maternal diet, neonatal inflammation

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