This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Google Scholar
Right arrow Articles by Assmann, A.
Right arrow Articles by Kulkarni, R. N.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Assmann, A.
Right arrow Articles by Kulkarni, R. N.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, June 2009, p. 3219-3228, Vol. 29, No. 11
0270-7306/09/$08.00+0     doi:10.1128/MCB.01489-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Glucose Effects on Beta-Cell Growth and Survival Require Activation of Insulin Receptors and Insulin Receptor Substrate 2{triangledown}

Anke Assmann,1,{dagger} Kohjiro Ueki,1,2,{dagger} Jonathon N. Winnay,1 Takahashi Kadowaki,2 and Rohit N. Kulkarni1*

Joslin Diabetes Center and Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts,1 Department of Metabolic Diseases, Graduate School of Medicine, University of Tokyo, Tokyo, Japan2

Received 23 September 2008/ Returned for modification 29 October 2008/ Accepted 20 February 2009

Insulin and insulin-like growth factor I (IGF-I) are ubiquitous hormones that regulate growth and metabolism of most mammalian cells, including pancreatic β-cells. In addition to being an insulin secretagogue, glucose regulates proliferation and survival of β-cells. However, it is unclear whether the latter effects of glucose occur secondary to autocrine activation of insulin signaling proteins by secreted insulin. To examine this possibility we studied the effects of exogenous glucose or insulin in β-cell lines completely lacking either insulin receptors (βIRKO) or insulin receptor substrate 2 (βIRS2KO). Exogenous addition of either insulin or glucose activated proteins in the insulin signaling pathway in control β-cell lines with the effects of insulin peaking earlier than glucose. Insulin stimulation of βIRKO and βIRS2KO cells led to blunted activation of phosphatidylinositol 3-kinase and Akt kinase, while surprisingly, glucose failed to activate either kinase but phosphorylated extracellular signal-regulated kinase. Control β-cells exhibited low expression of IGF-1 receptors compared to compensatory upregulation in βIRKO cells. The signaling data support the slow growth and reduced DNA and protein synthesis in βIRKO and βIRS2KO cells in response to glucose stimulation. Together, these studies provide compelling evidence that the growth and survival effects of glucose on β-cells require activation of proteins in the insulin signaling pathway.

* Corresponding author. Mailing address: Harvard Medical School, Joslin Diabetes Center, Room 602, One Joslin Place, Boston, MA 02215. Phone: (617) 713-3460. Fax: (617) 713-3476. E-mail: Rohit.Kulkarni{at}joslin.harvard.edu

{triangledown} Published ahead of print on 9 March 2009.

{dagger} A.A. and K.U. contributed equally to the report.

Molecular and Cellular Biology, June 2009, p. 3219-3228, Vol. 29, No. 11
0270-7306/09/$08.00+0     doi:10.1128/MCB.01489-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Bouzakri, K., Ribaux, P., Halban, P. A. (2009). Silencing Mitogen-activated Protein 4 Kinase 4 (MAP4K4) Protects Beta Cells from Tumor Necrosis Factor-{alpha}-induced Decrease of IRS-2 and Inhibition of Glucose-stimulated Insulin Secretion. J. Biol. Chem. 284: 27892-27898 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»