Journal Article

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

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

2013

Overview

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.

• Publisher: National Academy of Sciences,NATIONAL ACADEMY OF SCIENCES,National Acad Sciences
• Subject: Animals / autocrine signaling / Beta cells / Biological Sciences / calcium / Cell membranes / exocytosis / Female / Gestational diabetes / glucose / Glucose - metabolism / glucose tolerance / Immunoblotting / Immunohistochemistry / Insulin / Insulin - metabolism / Insulin Secretion / Insulin-Secreting Cells - drug effects / Insulin-Secreting Cells - metabolism / Islet cells / Islets of Langerhans / membrane potential / Mice / Mice, Inbred C57BL / Mice, Knockout / Microscopy, Fluorescence / Pregnancy / Receptors / Receptors, Serotonin, 5-HT3 - genetics / Receptors, Serotonin, 5-HT3 - metabolism / serotonin / Serotonin - pharmacology / Serotonin receptors / Signal Transduction - physiology