Submit a Letter to the Editor for:
Tadahiro Kitamura, Jun Nakae, Yukari Kitamura, Yoshiaki Kido, William H. Biggs III, Christopher V.E. Wright, Morris F. White, Karen C. Arden, Domenico Accili
J Clin Invest. 2002;
110(12):1839
doi:10.1172/JCI16857
Abstract |
Full text
|
PDF
D
iabetes is caused by an absolute (type 1) or relative (type 2) deficiency of insulin-producing β cells. The mechanisms governing replication of terminally differentiated β cells and neogenesis from progenitor cells are unclear. Mice lacking insulin receptor substrate-2 (Irs2) develop β cell failure, suggesting that insulin signaling is required to maintain an adequate β cell mass. We report that haploinsufficiency for the forkhead transcription factor Foxo1 reverses β cell failure in Irs2–/– mice through partial restoration of β cell proliferation and increased expression of the pancreatic transcription factor pancreas/duodenum homeobox gene-1 (Pdx1). Foxo1 and Pdx1 exhibit mutually exclusive patterns of nuclear localization in β cells, and constitutive nuclear expression of a mutant Foxo1 is associated with lack of Pdx1 expression. We show that Foxo1 acts as a repressor of Foxa2-dependent (Hnf-3β–dependent) expression from the Pdx1 promoter. We propose that insulin/IGFs regulate β cell proliferation by relieving Foxo1 inhibition of Pdx1 expression in a subset of cells embedded within pancreatic ducts.
Guidelines:
The Editorial Board will only consider letters that we deem relevant and of interest to our readers. We will not post data that have not been subjected to peer review, nor will we post letters that are essentially a reiteration of another letter. All accepted letters will be posted on our website within one week of acceptance. The Editors reserve the right to edit any letter for length, content, and clarity. Authors of all accepted letters will be asked to preview any changes. Authors will be notified by e-mail if their letters were not accepted. As this is a final decision, no appeals will be considered.
Specific requirements: All letters must be 400 words or fewer. You may enter the letter as plain text or HTML, if you wish. The author's name and e-mail address are required, and will be posted with the letter. All possible conflicts of interest must be noted, even if they are not posted. If you wish to include a figure (keep in mind that non-peer-reviewed data will not be posted), please contact the editor directly at editors@the-jci.org.
