| Serotonin regulates pancreatic beta cell mass during pregnancy. | |
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MedLine Citation:
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PMID: 20581837 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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During pregnancy, the energy requirements of the fetus impose changes in maternal metabolism. Increasing insulin resistance in the mother maintains nutrient flow to the growing fetus, whereas prolactin and placental lactogen counterbalance this resistance and prevent maternal hyperglycemia by driving expansion of the maternal population of insulin-producing beta cells. However, the exact mechanisms by which the lactogenic hormones drive beta cell expansion remain uncertain. Here we show that serotonin acts downstream of lactogen signaling to stimulate beta cell proliferation. Expression of serotonin synthetic enzyme tryptophan hydroxylase-1 (Tph1) and serotonin production rose sharply in beta cells during pregnancy or after treatment with lactogens in vitro. Inhibition of serotonin synthesis by dietary tryptophan restriction or Tph inhibition blocked beta cell expansion and induced glucose intolerance in pregnant mice without affecting insulin sensitivity. Expression of the G alpha(q)-linked serotonin receptor 5-hydroxytryptamine receptor-2b (Htr2b) in maternal islets increased during pregnancy and normalized just before parturition, whereas expression of the G alpha(i)-linked receptor Htr1d increased at the end of pregnancy and postpartum. Blocking Htr2b signaling in pregnant mice also blocked beta cell expansion and caused glucose intolerance. These studies reveal an integrated signaling pathway linking beta cell mass to anticipated insulin need during pregnancy. Modulators of this pathway, including medications and diet, may affect the risk of gestational diabetes. |
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Authors:
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Hail Kim; Yukiko Toyofuku; Francis C Lynn; Eric Chak; Toyoyoshi Uchida; Hiroki Mizukami; Yoshio Fujitani; Ryuzo Kawamori; Takeshi Miyatsuka; Yasuhiro Kosaka; Katherine Yang; Gerard Honig; Marieke van der Hart; Nina Kishimoto; Juehu Wang; Soroku Yagihashi; Laurence H Tecott; Hirotaka Watada; Michael S German |
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Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2010-06-27 |
Journal Detail:
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Title: Nature medicine Volume: 16 ISSN: 1546-170X ISO Abbreviation: Nat. Med. Publication Date: 2010 Jul |
Date Detail:
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Created Date: 2010-07-08 Completed Date: 2010-07-29 Revised Date: 2011-07-19 |
Medline Journal Info:
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Nlm Unique ID: 9502015 Medline TA: Nat Med Country: United States |
Other Details:
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Languages: eng Pagination: 804-8 Citation Subset: IM |
Affiliation:
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Diabetes Center, University of California-San Francisco, San Francisco, California, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Female Gene Expression Profiling Glucose / metabolism Insulin / metabolism Insulin-Secreting Cells / metabolism*, physiology Islets of Langerhans / physiology Mice Mice, Inbred C57BL Placental Lactogen / metabolism Pregnancy Pregnancy, Animal* Prolactin / metabolism Serotonin / metabolism* Tryptophan Hydroxylase / metabolism |
| Grant Support | |
ID/Acronym/Agency:
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P30 DK063720-04/DK/NIDDK NIH HHS; P30 DK063720-045954/DK/NIDDK NIH HHS; P30 DK063720-045955/DK/NIDDK NIH HHS; P30 DK063720-045956/DK/NIDDK NIH HHS; P30 DK063720-05/DK/NIDDK NIH HHS; P30 DK063720-057580/DK/NIDDK NIH HHS; P30 DK063720-059005/DK/NIDDK NIH HHS; P30 DK063720-06A1/DK/NIDDK NIH HHS; P30 DK063720-06A18402/DK/NIDDK NIH HHS; P30 DK063720-06A1S1/DK/NIDDK NIH HHS; P30 DK063720-07/DK/NIDDK NIH HHS; R01 DK021344-25/DK/NIDDK NIH HHS; R01 DK021344-26/DK/NIDDK NIH HHS; R01 DK021344-27A2/DK/NIDDK NIH HHS; R01 DK021344-28/DK/NIDDK NIH HHS; U19 DK061245-04/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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11061-68-0/Insulin; 50-67-9/Serotonin; 50-99-7/Glucose; 9002-62-4/Prolactin; 9035-54-5/Placental Lactogen; EC 1.14.16.4/TPH1 protein, human; EC 1.14.16.4/TPH2 protein, human; EC 1.14.16.4/Tph1 protein, mouse; EC 1.14.16.4/Tph2 protein, mouse; EC 1.14.16.4/Tryptophan Hydroxylase |
| Comments/Corrections | |
Comment In:
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Nat Med. 2010 Jul;16(7):756-7
[PMID:
20613752
]
Am J Transplant. 2011 May;11(5):877 [PMID: 21521461 ] |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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