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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.

Original publication




Journal article



Publication Date





1822 - 1835


Beta cell function, Calcium imaging, Diabetes, Hypothyroidism, Pancreas, Animals, Antithyroid Agents, Blood Glucose, Cell Proliferation, Diet, High-Fat, Disease Models, Animal, Female, Glucose Intolerance, Hyperinsulinism, Hypothyroidism, Insulin Resistance, Insulin-Secreting Cells, Iodine, Islets of Langerhans, Mice, Pregnancy, Pregnancy Complications, Prenatal Exposure Delayed Effects, Propylthiouracil, Stress, Physiological