The transcriptional response of the islet to pregnancy in mice

Sebastian Rieck, Peter White, Jonathan Schug, Alan J. Fox, Olga Smirnova, Nan Gao, Rana K Gupta, Zhao Wang, Philipp E Scherer, Mark P. Keller, Alan D. Attie, Klaus H. Kaestner

Research output: Contribution to journalArticle

104 Scopus citations

Abstract

The inability of the β-cell to meet the demand for insulin brought about by insulin resistance leads to type 2 diabetes. In adults, β-cell replication is one of the mechanisms thought to cause the expansion of β-cell mass. Efforts to treat diabetes require knowledge of the pathways that drive facultative β-cell proliferation in vivo. A robust physiological stimulus of β-cell expansion is pregnancy and identifying the mechanisms underlying this stimulus may provide therapeutic leads for the treatment of type 2 diabetes. The peak in β-cell proliferation during pregnancy occurs on d 14.5 of gestation in mice. Using advanced genomic approaches, we globally characterize the gene expression signature of pancreatic islets on d 14.5 of gestation during pregnancy. We identify a total of 1907 genes as differentially expressed in the islet during pregnancy. The islet's ability to compensate for relative insulin deficiency during metabolic stress is associated with the induction of both proliferative and survival pathways. A comparison of the genes induced in three different models of islet expansion suggests that diverse mechanisms can be recruited to expand islet mass. The identification of many novel genes involved in islet expansion during pregnancy provides an important resource for diabetes researchers to further investigate how these factors contribute to the maintenance of not only islet mass, but ultimately β-cell mass.

Original languageEnglish (US)
Pages (from-to)1702-1712
Number of pages11
JournalMolecular Endocrinology
Volume23
Issue number10
DOIs
StatePublished - 2009

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology

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    Rieck, S., White, P., Schug, J., Fox, A. J., Smirnova, O., Gao, N., Gupta, R. K., Wang, Z., Scherer, P. E., Keller, M. P., Attie, A. D., & Kaestner, K. H. (2009). The transcriptional response of the islet to pregnancy in mice. Molecular Endocrinology, 23(10), 1702-1712. https://doi.org/10.1210/me.2009-0144