Display Settings:

Format

Send to:

Choose Destination
Cell Rep. 2013 Feb 21;3(2):401-10. doi: 10.1016/j.celrep.2013.01.007. Epub 2013 Jan 31.

Liver-derived systemic factors drive β cell hyperplasia in insulin-resistant states.

Author information

  • 1Section of Islet Cell Biology and Regenerative Medicine, Joslin Diabetes Center and Harvard Medical School, Boston, MA 02115, USA.

Erratum in

  • Cell Rep. 2013 Mar 28;3(3):969.

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.

Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

PMID:
23375376
[PubMed - indexed for MEDLINE]
PMCID:
PMC3655439
Free PMC Article

Images from this publication.See all images (5)Free text

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science Icon for PubMed Central
    Loading ...
    Write to the Help Desk