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

Research output: Contribution to journalArticlepeer-review

122 Scopus citations


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 (US)
Pages (from-to)401-410
Number of pages10
JournalCell Reports
Issue number2
StatePublished - 2013
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • General Biochemistry, Genetics and Molecular Biology


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