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Proc Natl Acad Sci U S A. 2013 Nov 26;110(48):19420-5. doi: 10.1073/pnas.1310953110. Epub 2013 Nov 11.

Serotonin regulates glucose-stimulated insulin secretion from pancreatic β cells during pregnancy.

Author information

1
Departments of Biochemistry and Cell Physiology Kyorin University School of Medicine, Mitaka, Tokyo 181-8611, Japan.

Abstract

In preparation for the metabolic demands of pregnancy, β cells in the maternal pancreatic islets increase both in number and in glucose-stimulated insulin secretion (GSIS) per cell. Mechanisms have been proposed for the increased β cell mass, but not for the increased GSIS. Because serotonin production increases dramatically during pregnancy, we tested whether flux through the ionotropic 5-HT3 receptor (Htr3) affects GSIS during pregnancy. Pregnant Htr3a(-/-) mice exhibited impaired glucose tolerance despite normally increased β cell mass, and their islets lacked the increase in GSIS seen in islets from pregnant wild-type mice. Electrophysiological studies showed that activation of Htr3 decreased the resting membrane potential in β cells, which increased Ca(2+) uptake and insulin exocytosis in response to glucose. Thus, our data indicate that serotonin, acting in a paracrine/autocrine manner through Htr3, lowers the β cell threshold for glucose and plays an essential role in the increased GSIS of pregnancy.

PMID:
24218571
PMCID:
PMC3845121
DOI:
10.1073/pnas.1310953110
[Indexed for MEDLINE]
Free PMC Article

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