Interaction entre facteurs d’environnement et fonds génétique dans le diabète de type 2

Bernard, Catherine; Zuana, Odile Della; Ktorza, Alain

doi:10.1051/medsci/2013298020

Cited by 2 publications

(4 citation statements)

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“…First, pre-existing metabolic disorders, such as malnutrition, obesity and diabetes, have been linked to increased susceptibility of the offspring to chronic diseases, such as hypertension and diabetes [7,8]. In mice, maternal diabetes induces fetal hyperglycaemia and hyperinsulinaemia through accelerated endocrine pancreas development, predisposing to type 2 diabetes at later stages [9]. Second, gestation itself leads to important metabolic and hormonal modifications.…”

Section: Introductionmentioning

confidence: 99%

“…Second, gestation itself leads to important metabolic and hormonal modifications. For instance, gestational diabetes, occurring in 13% of pregnancies [10], alters endocrine pancreas maturation in the fetus and constitutes a risk factor for type 2 diabetes in adulthood [9]. In addition, gestation increases demand on thyroid hormones in the mother, leading to hypothyroidism in 0.5% of pregnancies [11].…”

Section: Introductionmentioning

confidence: 99%

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Maternal hypothyroidism in mice influences glucose metabolism in adult offspring

et al. 2020

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Aims/hypothesis During pregnancy, maternal metabolic disease and hormonal imbalance may alter fetal beta cell development and/or proliferation, thus leading to an increased risk for developing type 2 diabetes in adulthood. Although thyroid hormones play an important role in fetal endocrine pancreas development, the impact of maternal hypothyroidism on glucose homeostasis in adult offspring remains poorly understood. Methods We investigated this using a mouse model of hypothyroidism, induced by administration of an iodine-deficient diet supplemented with propylthiouracil during gestation. Results Here, we show that, when fed normal chow, adult mice born to hypothyroid mothers were more glucose-tolerant due to beta cell hyperproliferation (two- to threefold increase in Ki67-positive beta cells) and increased insulin sensitivity. However, following 8 weeks of high-fat feeding, these offspring gained 20% more body weight, became profoundly hyperinsulinaemic (with a 50% increase in fasting insulin concentration), insulin-resistant and glucose-intolerant compared with controls from euthyroid mothers. Furthermore, altered glucose metabolism was maintained in a second generation of animals. Conclusions/interpretation Therefore, gestational hypothyroidism induces long-term alterations in endocrine pancreas function, which may have implications for type 2 diabetes prevention in affected individuals.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Maternal hypothyroidism in mice influences glucose metabolism in adult offspring

et al. 2020

View full text Add to dashboard Cite

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“…First, pre-existing metabolic disorders, such as malnutrition, obesity and diabetes, have been linked to increased susceptibility of the offsprings to chronic diseases, such as hypertension and diabetes (7,8). In mice, maternal diabetes induces fetal hyperglycemia and hyperinsulinemia through accelerated endocrine pancreas development, predisposing to T2D at later stages (9). Second, gestation itself leads to important metabolic and hormonal modifications.…”

Section: Introductionmentioning

confidence: 99%

“…Second, gestation itself leads to important metabolic and hormonal modifications. For instance, gestational diabetes, occurring in 13 % of pregnancies (10), alters endocrine pancreas maturation in the fetus and constitutes a risk factor for T2D in adulthood (9). In addition, gestation increases demand on thyroid hormones in the mother, leading to hypothyroidism in 0.5 % of pregnancies (11).…”

Section: Introductionmentioning

confidence: 99%

Maternal hypothyroidism in mice influences glucose metabolism in adult offspring

Kemkem

Nasteska

Bray

et al. 2019

Preprint

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Running title: transgenerational effect of gestational hypothyroidism on beta cell function SIGNIFICANCE Diabetes and hypothyroidism are two major public health issues, affecting ~ 9 and 2 % of the population worldwide, respectively. As master metabolic gatekeepers, the thyroid hormones play an essential role in metabolism and fetal development. However, gestation increases demand on the thyroid axis in the mother, leading to hypothyroidism in 0.5 % of pregnancies.Maternal hypothyroidism is associated with deficits in fetal growth that may lead to long-term alterations in metabolism in the offspring. We therefore sought to investigate the effects of gestational hypothyroidism on glucose metabolism in adult offspring and their descendants, and how this may predispose to diabetes development. ABSTRACTDuring pregnancy, maternal metabolic diseases and hormonal imbalance may alter fetal beta cell development and/or proliferation, thus leading to an increased risk for developing type 2 diabetes in adulthood. Although thyroid hormones play an important role in fetal endocrine pancreas development, the impact of maternal hypothyroidism on glucose homeostasis in adult offsprings remains poorly understood. Here, we show that when fed normal chow, adult mice born to hypothyroid mothers were more glucose-tolerant due to beta cell hyperproliferation and increased insulin sensitivity. However, following high fat feeding, these offsprings became profoundly hyperinsulinemic, insulin-resistant and glucose-intolerant compared to controls from euthyroid mothers. Suggesting presence of epigenetic changes, altered glucose metabolism was maintained in a second generation of animals. As such, gestational hypothyroidism induces long-term and persistent alterations in endocrine pancreas function, which may have important implications for type 2 diabetes prevention in affected individuals.

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Interaction entre facteurs d’environnement et fonds génétique dans le diabète de type 2

Cited by 2 publications

References 49 publications

Maternal hypothyroidism in mice influences glucose metabolism in adult offspring

Maternal hypothyroidism in mice influences glucose metabolism in adult offspring

Maternal hypothyroidism in mice influences glucose metabolism in adult offspring

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