E-GEOD-21860 - RNA-seq of pancreatic islets from pregnant mice

Status
Released on 1 July 2010, last updated on 30 April 2015
Organism
Mus musculus
Samples (6)
Protocols (5)
Description
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, while 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 drive beta-cell proliferation. Serotonin synthetic enzyme Tph1 and serotonin production increased 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 Gq-linked serotonin receptor Htr2b in maternal islets increased during pregnancy and normalized just prior to parturition, while expression of the Gi-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. Analysis of poly(A)+ RNA from 3 biological replicates of pancreatic islets isolated from normal female and pregnant female mice
Experiment type
RNA-seq of coding RNA 
Contacts
Hail Kim <geo@ncbi.nlm.nih.gov>, Francis F Lynn, Michael S German
Citation
Serotonin regulates pancreatic beta cell mass during pregnancy. Kim H, Toyofuku Y, Lynn FC, Chak E, Uchida T, Mizukami H, Fujitani Y, Kawamori R, Miyatsuka T, Kosaka Y, Yang K, Honig G, van der Hart M, Kishimoto N, Wang J, Yagihashi S, Tecott LH, Watada H, German MS.
MINSEQE
Exp. designProtocolsVariablesProcessedSeq. reads
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