Thyroxine induces pancreatic beta cell apoptosis in rats

Diabetologia. 2002 Jun;45(6):851-5. doi: 10.1007/s00125-002-0842-5. Epub 2002 May 17.


Aims/hypothesis: Thyroid hormones reduce glucose tolerance in animals and humans. This effect is accompanied by a reduction in the beta-cell volume of the pancreas.

Methods: We studied the underlying mechanism using terminal UTP nick end labelling (TUNEL) and caspase-3 to analyse apoptosis and BrdU labelling of beta-cell proliferation.

Results: The reason for the reduction of the beta-cell volume of the pancreas after thyroxine treatment is apparently an increased rate of beta-cell apoptosis by an increase of TUNEL and caspase-3 positive rat beta cells. In parallel, thyroxine treatment increased the rate of apoptosis in rat pancreatic ductal cells which are considered to contribute to the pool of stem cells from which insulin-producing beta cells originate. The effects of thyroid hormone treatment are reversible through an increase of the beta-cell replication rate when thyroxine is withdrawn as documented by an increase of the BrdU labelling index.

Conclusion/interpretation: An increased rate of beta-cell death due to apoptosis causes a decrease of insulin content and glucose-induced insulin secretion from the pancreas in hyperthyroidism. The resulting reduction of beta cells in the pancreas can provide an explanation for the decrease of glucose tolerance in hyperthyroidism.

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Caspase 3
  • Caspases / metabolism
  • Cell Division / drug effects
  • In Situ Nick-End Labeling
  • Islets of Langerhans / cytology
  • Islets of Langerhans / drug effects
  • Islets of Langerhans / physiology*
  • Rats
  • Thyroxine / pharmacology*


  • Casp3 protein, rat
  • Caspase 3
  • Caspases
  • Thyroxine