Gluten-free diet during pregnancy alleviates signs of diabetes and celiac disease in NOD mouse offspring

Martin Haupt-Jorgensen, Jesper Larsen, Knud Josefsen, Tina Z Jørgensen, Julie Christine Antvorskov, Axel K Hansen, Karsten Buschard

Abstract

BACKGROUND: Gluten-free (GF) diet during pregnancy ameliorates autoimmune diabetes in nonobese diabetic (NOD) mouse offspring. Due to comorbidity of celiac disease in type 1 diabetes, we hypothesized that GF diet in utero alleviates the humoral and histopathological signs of celiac disease in NOD mice. We aimed to establish the mechanisms behind the diabetes-protective effect of GF diet in utero.

METHODS: Breeding pairs of NOD mice were fed a GF or gluten-containing standard (STD) diet until parturition. The offspring were nursed by mothers on STD diet and continued on this diet until ages 4 and 13 weeks. Analyses of serum antitissue transglutaminase (anti-tTG) intestine and islet histology, islet transglutaminase (TG) activity, and cytokine expression in T cells from lymphoid organs were performed.

RESULTS: GF versus STD diet in utero led to reduced serum anti-tTG titre and increased villus-to-crypt ratio at both ages. Insulitis along with systemic and local inflammation were decreased, but islet TG activity was unchanged in 13-week-old GF mice. These mice had unchanged beta-cell volumes, but increased islet numbers throughout the prediabetic period.

CONCLUSIONS: Collectively, GF diet administered during pregnancy improves signs of celiac disease and autoimmune diabetes in the offspring. The diabetes-ameliorative effect of GF diet in utero is followed by dampening of inflammation, unchanged beta-cell volume, but increased islet numbers.

OriginalsprogEngelsk
TidsskriftDiabetes - Metabolism: Research and Reviews (Print Edition)
Vol/bind34
Udgave nummer4
Sider (fra-til)e2987
ISSN1520-7552
DOI
StatusUdgivet - maj 2018

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