"We had shown that islet cells had all the 'machinery' for producing serotonin, but we thought it was coincidental," German said. "What this paper shows is not only does the gene for synthesizing serotonin increase, but also the amount of serotonin in the beta cells increases 1,000-fold during pregnancy."

Beta cells are the specific islet cells that produce and release insulin and make up the majority of the cells found in the part of the pancreas known as the islets of Langerhans.

Why that happened was the next question. German said the amount of serotonin rises in the bloodstream during pregnancy, but only by about 50 percent. The magnitude of this change, in comparison, indicated that it had a local use.

"We looked to see whether beta cells have receptors for serotonin, and in fact they do," he said. "We realized that this must be controlling beta cell proliferation."

Sure enough, German added, anything the lab did to inhibit production of serotonin by islet cells, including restricting tryptophan in the diet, caused the cells to stop proliferating and led to gestational diabetes in the mice.

The researchers discovered that as the hormone prolactin increases at the onset of pregnancy, it activates the gene that produces Tph1 in beta cells. That stimulates serotonin receptors and causes beta cells to proliferate, generating the increase in insulin.

The research indicates that modulators of the serotonin pathway, including drugs, diet and genetic inheritance, may affect the risk of gestational diabetes and, possibly, the long-term risk of developing type 2 diabetes, according to the researchers. The dual roles of serotonin in regulating mood and beta cell mass also could explain the association of depression with both type 2 diabetes and gestational diabetes, as well as the effects of some classes of psychiatric medications on diabetes. The researchers noted that a more complete understanding of the function of this pathway could suggest improved methods for both preventing and treating diabetes.

Source: University of California - San Francisco