Details

Autor(en) / Beteiligte

• Ohara-Imaizumi, Mica
• Kim, Hail
• Yoshida, Masashi
• Fujiwara, Tomonori
• Aoyagi, Kyota
• Toyofuku, Yukiko
• Nakamichi, Yoko
• Nishiwaki, Chiyono
• Okamura, Tadashi
• Uchida, Toyoyoshi
• Fujitani, Yoshio
• Akagawa, Kimio
• Kakei, Masafumi
• Watada, Hirotaka
• German, Michael S.
• Nagamatsu, Shinya

Titel

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

Ist Teil von

• Proceedings of the National Academy of Sciences - PNAS, 2013-11, Vol.110 (48), p.19420-19425

Ort / Verlag

United States: National Academy of Sciences

Erscheinungsjahr

2013

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.