Pancreatic Islet Cells Express Serotonergic Genes in Mice
Serotonergic transcription factor also binds to insulin gene regulatory element in β-cells
THURSDAY, Oct. 27 (HealthDay News) -- Pancreatic islet cells express all the genes responsible for synthesis, packaging, and secretion of serotonin, including the serotonergic transcription factor Pet1, according to an experimental study published online Oct. 19 in Diabetes.
Yasuharu Ohta, from the University of California in San Francisco, and colleagues investigated whether the developmental parallels between pancreatic islet cells and serotonin-producing neurons in the hind brain had any functional consequences. The expressions and functions of key serotonergic genes in the pancreas were assessed using transcriptional profiling, immunochemistry, DNA-binding analyses, and mouse genetic models.
The investigators found that the genes encoding all of the requisite products for the synthesis, packaging, and secretion of serotonin were expressed by islet cells, including both isoforms of the serotonin synthetic enzyme tryptophan hydroxylase, and the serotonergic transcription factor Pet1. As seen in serotonergic neurons, homeodomain transcription factor Nkx2.2, but not Nkx6.1, was required for Pet1 expression in islets. Pet1 bound to serotonergic genes as well as to a conserved insulin gene regulatory element in β-cells. Mice lacking Pet1 showed impaired glucose tolerance and reduced insulin production and secretion.
"A common transcriptional cascade drives the differentiation of β-cells and serotonergic neurons and imparts the shared ability to produce serotonin," the authors write.