Liver-Derived Systemic Factors Drive β Cell Hyperplasia in Insulin-Resistant States

Abdelfattah El Ouaamari, Dan Kawamori, Ercument Dirice, Chong Wee Liew, Jennifer L. Shadrach, Jiang Hu, Hitoshi Katsuta, Jennifer Hollister-Lock, Wei Jun Qian, Amy J. Wagers, Rohit N. Kulkarni

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Abstract

Integrative organ crosstalk regulates key aspects of energy homeostasis, and its dysregulation may underlie metabolic disorders such as obesity and diabetes. To test the hypothesis that crosstalk between the liver and pancreatic islets modulates β cell growth in response to insulin resistance, we used the liver-specific insulin receptor knockout (LIRKO) mouse, a unique model that exhibits dramatic islet hyperplasia. Using complementary in vivo parabiosis and transplantation assays, as well as in vitro islet culture approaches, we demonstrate that humoral, nonneural, non-cell-autonomous factor(s) induces β cell proliferation in LIRKO mice. Furthermore, we report that a hepatocyte-derived factor(s) stimulates mouse and human β cell proliferation in ex vivo assays, independent of ambient glucose and insulin levels. These data implicate the liver as a critical source of β cell growth factor(s) in insulin-resistant states.

Original languageEnglish
Pages (from-to)401-410
Number of pages10
JournalCell Reports
Volume3
Issue number2
DOIs
Publication statusPublished - Feb 1 2013
Externally publishedYes

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All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

El Ouaamari, A., Kawamori, D., Dirice, E., Liew, C. W., Shadrach, J. L., Hu, J., ... Kulkarni, R. N. (2013). Liver-Derived Systemic Factors Drive β Cell Hyperplasia in Insulin-Resistant States. Cell Reports, 3(2), 401-410. https://doi.org/10.1016/j.celrep.2013.01.007