TY  - JOUR
A1  - Keller, Mark P.
A1  - Choi, YounJeong
A1  - Wang, Ping
A1  - Belt Davis, Dawn
A1  - Rabaglia, Mary E.
A1  - Oler, Angie T.
A1  - Stapleton, Donald S.
A1  - Argmann, Carmen
A1  - Schueler, Kathy L.
A1  - Edwards, Steve
A1  - Steinberg, H. Adam
A1  - Chaibub Neto, Elias
A1  - Kleinhanz, Robert
A1  - Turner, Scott
A1  - Hellerstein, Marc K.
A1  - Schadt, Eric E.
A1  - Yandell, Brian S.
A1  - Kendziorski, Christina
A1  - Attie, Alan D.
T1  - A gene expression network model of type 2 diabetes links cell cycle regulation in islets with diabetes susceptibility
Y1  - 2008/05/01 
JF  - Genome Research 
JO  - Genome Research 
SP  - 706 
EP  - 716 
DO  - 10.1101/gr.074914.107 
VL  - 18 
IS  - 5 
UR  - http://genome.cshlp.org/content/18/5/706.abstract 
N2  - Insulin resistance is necessary but not sufficient for the development of type 2 diabetes. Diabetes results when pancreatic beta-cells fail to compensate for insulin resistance by increasing insulin production through an expansion of beta-cell mass or increased insulin secretion. Communication between insulin target tissues and beta-cells may initiate this compensatory response. Correlated changes in gene expression between tissues can provide evidence for such intercellular communication. We profiled gene expression in six tissues of mice from an obesity-induced diabetes-resistant and a diabetes-susceptible strain before and after the onset of diabetes. We studied the correlation structure of mRNA abundance and identified 105 co-expression gene modules. We provide an interactive gene network model showing the correlation structure between the expression modules within and among the six tissues. This resource also provides a searchable database of gene expression profiles for all genes in six tissues in lean and obese diabetes-resistant and diabetes-susceptible mice, at 4 and 10 wk of age. A cell cycle regulatory module in islets predicts diabetes susceptibility. The module predicts islet replication; we found a strong correlation between 2H2O incorporation into islet DNA in vivo and the expression pattern of the cell cycle module. This pattern is highly correlated with that of several individual genes in insulin target tissues, including Igf2, which has been shown to promote beta-cell proliferation, suggesting that these genes may provide a link between insulin resistance and beta-cell proliferation. 
ER  -