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


ABSTRACT: In preparation for the metabolic demands of pregnancy, ? 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 ? 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 ? 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 ? 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 ? cell threshold for glucose and plays an essential role in the increased GSIS of pregnancy.

SUBMITTER: Ohara-Imaizumi M 

PROVIDER: S-EPMC3845121 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature

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

Ohara-Imaizumi Mica M   Kim Hail H   Yoshida Masashi M   Fujiwara Tomonori T   Aoyagi Kyota K   Toyofuku Yukiko Y   Nakamichi Yoko Y   Nishiwaki Chiyono C   Okamura Tadashi T   Uchida Toyoyoshi T   Fujitani Yoshio Y   Akagawa Kimio K   Kakei Masafumi M   Watada Hirotaka H   German Michael S MS   Nagamatsu Shinya S  

Proceedings of the National Academy of Sciences of the United States of America 20131111 48


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 tole  ...[more]

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