The discovery could lead to simple dietary solutions and possible therapeutics for gestational diabetes, which if untreated, has serious implications for both mother and child.
Scientists have puzzled for decades over the fact that the onset of pregnancy causes a woman to double the number of insulin-producing islet cells in her pancreas, according to Professor Michael German, senior author of the paper. Until now, no one has known what caused that change.
Using a genomic analysis of both pregnant and non-pregnant mice, the researchers conducted a scan of all of the genes that were turned either on or off during pregnancy. At the top of the list was tryptophan hydroxylase (Tph1), the enzyme that produces serotonin from the amino acid tryptophan. In the newly pregnant mice, that enzyme rose exponentially.
“This is really novel,” said German. “This was not an expected finding and we really stumbled upon it. To see a gene go up 1,000-fold that we didn’t know was involved is very rewarding.” Because serotonin is made from tryptophan this result also provides a clear link between the amount and type of protein consumed by the mother early in pregnancy and the generation of islet cells needed to protect her against gestational diabetes late in pregnancy.
Serotonin has been widely studied for its effects on appetite and mood. Due to similarities between the insulin producing cells in the pancreas and certain types of neurons in the brain, German’s laboratory had been collaborating with two faculty members in the Department of Psychiatry. Together, the three had been studying the developmental and functional similarities between serotonin-producing brain cells and insulin-producing cells.
“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 islets of Langerhans.
“We looked to see whether beta cells have receptors for serotonin, and in fact they do,” German said. “We realized that this must be controlling beta cell proliferation.” 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.
MEDICA.de; Source: University of California, San Francisco