Effect of thyroid hormones on Pancreatic B cell function
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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.