A gene expression network model of type 2 diabetes links cell cycle regulation in islets with diabetes susceptibility

被引：279

作者：

Keller, Mark P. ^{[1
]}

Choi, YounJeong ^{[2
,3
]}

Wang, Ping ^{[2
,3
]}

Davis, Dawn Belt ^{[1
]}

Rabaglia, Mary E. ^{[1
]}

Oler, Angie T. ^{[1
]}

Stapleton, Donald S. ^{[1
]}

Argmann, Carmen ^{[4
]}

Schueler, Kathy L. ^{[1
]}

Edwards, Steve ^{[4
]}

Steinberg, H. Adam ^{[1
]}

Chaibub Neto, Elias ^{[3
]}

Kleinhanz, Robert ^{[4
]}

Turner, Scott ^{[5
]}

Hellerstein, Marc K. ^{[6
,7
]}

Schadt, Eric E. ^{[4
]}

Yandell, Brian S. ^{[2
,3
,8
]}

Kendziorski, Christina ^{[2
]}

Attie, Alan D. ^{[1
]}

机构：

[1] Univ Wisconsin, Dept Chem, Madison, WI 53076 USA

[2] Univ Wisconsin, Dept Biostat & Med Informat, Madison, WI 53076 USA

[3] Univ Wisconsin, Dept Stat, Madison, WI 53076 USA

[4] Rosetta Inpharmat, Seattle, WA 98109 USA

[5] KineMed, Emeryville, CA 94608 USA

[6] Univ Calif Berkeley, Dept Nutr Sci & Toxicol, Berkeley, CA 94720 USA

[7] Univ Calif San Francisco, Dept Med, Div Endocrinol & Metab, San Francisco, CA 94110 USA

[8] Univ Wisconsin, Dept Hort, Madison, WI 53076 USA

来源：

GENOME RESEARCH | 2008年 / 18卷 / 05期

关键词：

D O I：

10.1101/gr.074914.107

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 (H2O)-H-2 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.

引用

页码：706 / 716

页数：11

共 48 条

[1] All β cells contribute equally to islet growth and maintenance [J].