title: Liver-derived systemic factors drive β cell hyperplasia in insulin-resistant states.
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.
authors: Section of Islet Cell Biology and Regenerative Medicine, Joslin Diabetes Center and Harvard Medical School, Boston, MA 02115, USA.
authors: Abdelfattah
authors: A
authors: El Ouaamari
authors: Dan
authors: D
authors: Kawamori
authors: Ercument
authors: E
authors: Dirice
authors: Chong Wee
authors: CW
authors: Liew
authors: Jennifer L
authors: JL
authors: Shadrach
authors: Jiang
authors: J
authors: Hu
authors: Hitoshi
authors: H
authors: Katsuta
authors: Jennifer
authors: J
authors: Hollister-Lock
authors: Wei-Jun
authors: WJ
authors: Qian
authors: Amy J
authors: AJ
authors: Wagers
authors: Rohit N
authors: RN
authors: Kulkarni
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D017077:Culture Media, Conditioned; D022781:Hepatocytes / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D006965:Hyperplasia; D007333:Insulin Resistance; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000187:drug effects*; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology*; D007515:Islets of Langerhans / Q000378:metabolism / Q000473:pathology*; D016381:Islets of Langerhans Transplantation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011972:Receptor, Insulin / Q000172:deficiency / Q000235:genetics / Q000378:metabolism
chemical_list: D017077:Culture Media, Conditioned; D036341:Intercellular Signaling Peptides and Proteins; D011972:Receptor, Insulin
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