title: The transcriptional response of the islet to pregnancy in mice.
abstract: The inability of the ss-cell to meet the demand for insulin brought about by insulin resistance leads to type 2 diabetes. In adults, ss-cell replication is one of the mechanisms thought to cause the expansion of ss-cell mass. Efforts to treat diabetes require knowledge of the pathways that drive facultative ss-cell proliferation in vivo. A robust physiological stimulus of ss-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 ss-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 ss-cell mass.
authors: Department of Genetics and Institute for Diabetes, Obesity and Metabolism, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6145, USA.
authors: Sebastian
authors: S
authors: Rieck
authors: Peter
authors: P
authors: White
authors: Jonathan
authors: J
authors: Schug
authors: Alan J
authors: AJ
authors: Fox
authors: Olga
authors: O
authors: Smirnova
authors: Nan
authors: N
authors: Gao
authors: Rana K
authors: RK
authors: Gupta
authors: Zhao V
authors: ZV
authors: Wang
authors: Philipp E
authors: PE
authors: Scherer
authors: Mark P
authors: MP
authors: Keller
authors: Alan D
authors: AD
authors: Attie
authors: Klaus H
authors: KH
authors: Kaestner
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D048429:Cell Size; D002470:Cell Survival; D004195:Disease Models, Animal; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006984:Hypertrophy; D050417:Insulin-Secreting Cells / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D009765:Obesity / Q000473:pathology; D011247:Pregnancy; D015398:Signal Transduction; D013997:Time Factors; D014158:Transcription, Genetic