Serotonin regulates glucose-stimulated insulin secretion from pancreatic β cells during pregnancy.
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.
Departments of Biochemistry and Cell Physiology Kyorin University School of Medicine, Mitaka, Tokyo 181-8611, Japan.
Mica
M
Ohara-Imaizumi
Hail
H
Kim
Masashi
M
Yoshida
Tomonori
T
Fujiwara
Kyota
K
Aoyagi
Yukiko
Y
Toyofuku
Yoko
Y
Nakamichi
Chiyono
C
Nishiwaki
Tadashi
T
Okamura
Toyoyoshi
T
Uchida
Yoshio
Y
Fujitani
Kimio
K
Akagawa
Masafumi
M
Kakei
Hirotaka
H
Watada
Michael S
MS
German
Shinya
S
Nagamatsu
D000818:Animals; D005260:Female; D005947:Glucose / Q000378:metabolism; D015151:Immunoblotting; D007150:Immunohistochemistry; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008856:Microscopy, Fluorescence; D011247:Pregnancy; D044406:Receptors, Serotonin, 5-HT3 / Q000235:genetics / Q000378:metabolism*; D012701:Serotonin / Q000494:pharmacology*; D015398:Signal Transduction / Q000502:physiology*
D007328:Insulin; D044406:Receptors, Serotonin, 5-HT3; D012701:Serotonin; D005947:Glucose