Maternal hypothyroidism in mice influences glucose metabolism in adult offspring

Diabetologia. 2020 Sep;63(9):1822-1835. doi: 10.1007/s00125-020-05172-x. Epub 2020 May 30.


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.

Keywords: Beta cell function; Calcium imaging; Diabetes; Hypothyroidism; Pancreas.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antithyroid Agents / toxicity
  • Blood Glucose / metabolism*
  • Cell Proliferation
  • Diet, High-Fat
  • Disease Models, Animal
  • Female
  • Glucose Intolerance / metabolism*
  • Hyperinsulinism / metabolism
  • Hypothyroidism / metabolism*
  • Insulin Resistance
  • Insulin-Secreting Cells / metabolism*
  • Iodine / deficiency
  • Islets of Langerhans / embryology*
  • Islets of Langerhans / metabolism
  • Mice
  • Pregnancy
  • Pregnancy Complications / metabolism*
  • Prenatal Exposure Delayed Effects / metabolism*
  • Propylthiouracil / toxicity
  • Stress, Physiological


  • Antithyroid Agents
  • Blood Glucose
  • Propylthiouracil
  • Iodine