Hyperthyroidism is known to impair glucose tolerance, but possible
direct effects of thyroid hormones on the insulin producing b cell of the
islets of Langerhans have not previously been reported. Experiments have been
performed to investigate the interactions between thyroid hormones and rat
pancreatic islets Hn vitro ', using a tissue culture system to maintain the
stability of the extracellular environment. The secondary effects, of hyper¬
thyroidism on pancreatic hormone secretion were thereby excluded.
Thyroxine had no effect on insulin secretion from isolated islets during
one hour incubations. However, after 24 hour tissue culture of islets in the
presence of thyroid.hormones, both insulin biosynthesis and secretion v/ere
significantly reduced in response to higher concentrations of glucose.
Theophylline fully restored insulin release to normal levels. The ultrastructure
and insulin content of islets were not altered by 24 hour exposure to thyroid
hormones, despite a significant inhibition of protein synthesis and a 20%
reduction in total islet protein. Thyroid hormones did not affect the
activity of islet adenylate cyclase. Thyroid hormones may thus contribute to the glucose intolerance observed
in hyperthyroid states, in part by a direct action on pancreatic B cell meta¬
bolism, and a consequent inhibition of insulin biosynthesis and secretion.
These effects could be a result of a thyroid hormone-induced increase of Na K -
ATPase activity, with the possible effects on intracellular cyclic AMP concen¬
trations, translocation of cations across the plasma membrane and accumulation
of cytosolic calcium.
To overcome the problem of poor islet yield from the pancreas, rats were
pretre3ted with pilocarpine, as described in the Appendix, This significantly
enhanced islet yield, but the islets were unsuitable tor metabolic studies due
to their depleted insulin content. However, long-term islet viability was not
altered, and they were used successfully for transplantation experiments
