Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2009 Oct;23(10):1702-12.
doi: 10.1210/me.2009-0144. Epub 2009 Jul 2.

The transcriptional response of the islet to pregnancy in mice

Sebastian Rieck  1 , Peter White, Jonathan Schug, Alan J Fox, Olga Smirnova, Nan Gao, Rana K Gupta, Zhao V Wang, Philipp E Scherer, Mark P Keller, Alan D Attie, Klaus H Kaestner
Affiliations

The transcriptional response of the islet to pregnancy in mice

Sebastian Rieck et al. Mol Endocrinol. 2009 Oct.

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.

PubMed Disclaimer

Figures

Figure 1
Figure 1
ß-Cell proliferation with ß-cell hypertrophy dramatically increase ß-cell mass at d 14.5 of pregnancy in mice. A, ß-Cell mass of nonpregnant and pregnant (d 14.5) mice (n = 3–4/group; *, P < 0.05 vs. nonpregnant control). Quantification of (B) BrdU-positive cells per islet (n = 4–5; *, P < 0.03 vs. control), (C) BrdU-positive cells as % of total nuclei (n = 4–5; *P < 0.01 vs. control), and (D) percentage of islets with certain number of BrdU-positive cells. Determination of (E) ß-cell size and (F) percentage of islets with certain ß-cell size (n = 4–5; *, P < 0.05 vs. control). Gene expression changes (G) of cell cycle regulators (n = 4–5; *, P < 0.05 vs. control). AU, Arbitrary units; pos., positive.
Figure 2
Figure 2
Histological analysis of ß-cell proliferation, hypertrophy, and mass at d 14.5 during pregnancy. Insulin staining (A) and BrdU incorporation into ß-cells (C) of pregnant mice, insulin (B) and BrdU (D) staining of nonpregnant female mice, and BrdU staining of pregnant (E) and nonpregnant (F) mice (×20). Ki67 staining of pregnant (G), and nonpregnant (H) mice, dual fluorescent staining of cell surface marker E-cadherin (red) and insulin (green) of pregnant (I) and nonpregnant (J) mice.
Figure 3
Figure 3
Temporal gene expression analysis of selected differentially expressed genes throughout pregnancy. A–R, Gene expression changes for each respective gene during d 10.5, d 14.5, and d 18.5 during pregnancy (n = 4–5 per time point; *, P < 0.05; #, P < 0.09).
Figure 4
Figure 4
Differentially expressed genes identified in the islet are expressed in ß-cells during pregnancy d 14.5. Gene expression changes for insulin (A) and Pdx1 (B) in wild-type liver, pregnant d 14.5 GFP− and pregnant day 14.5 GFP+ single-cell fractions. C–O, Gene expression levels of selected genes in pregnant d 14.5 GFP− compared with pregnant d 14.5 GFP+ single-cell fractions (n = 3 per fraction; *, P < 0.05).
Figure 5
Figure 5
Gene expression profiles differ between the pregnancy, obesity, and ß-cell injury models of ß-cell regeneration. A, Strain-dependent comparison of mRNA expression of both mKi67 and Birc5 between both 4- and 10-wk-old B6ob/ob and BTBRob/ob leptin-deficient mice and lean controls (n = 5–7 per strain; *, P < 0.05 vs. respective lean control; #, P = 0.055; $, P = 0.08). B, Expression of selected differentially expressed genes identified in the pregnancy paradigm during obesity at 10 wk in the B6 strain (n = 5–7 per strain; *, P < 0.05 vs. lean control; &, not detectable). C, Temporal gene expression of mKi67 and Birc5 before (d 0), after (d 30), and during (d 8) recovery from chemically induced ß-cell ablation. D and E, Temporal gene expression of selected pregnancy-induced genes during recovery from chemically induced ß-cell ablation in the PANIC-ATTAC model (n = 4–5 per time point; *, P < 0.05 vs. day 0).
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Butler AE, Janson J, Bonner-Weir S, Ritzel R, Rizza RA, Butler PC 2003 β-Cell deficit and increased β-cell apoptosis in humans with type 2 diabetes. Diabetes 52:102–110 - PubMed
    1. Heit JJ, Karnik SK, Kim SK 2006 Intrinsic regulators of pancreatic β-cell proliferation. Annu Rev Cell Dev Biol 22:311–338 - PubMed
    1. Bonner-Weir S, Weir GC 2005 New sources of pancreatic β-cells. Nat Biotechnol 23:857–861 - PubMed
    1. Dor Y, Brown J, Martinez OI, Melton DA 2004 Adult pancreatic β-cells are formed by self-duplication rather than stem-cell differentiation. Nature 429:41–46 - PubMed
    1. Xu X, D'Hoker J, Stangé G, Bonné S, De Leu N, Xiao X, Van de Casteele M, Mellitzer G, Ling Z, Pipeleers D, Bouwens L, Scharfmann R, Gradwohl G, Heimberg H 2008 β-Cells can be generated from endogenous progenitors in injured adult mouse pancreas. Cell 132:197–207 - PubMed

Publication types