HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text (PDF) Online-Only Appendix All Versions of this Article: db06-1513v1 56/7/1792    most recent Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Alonso, L. C. Articles by Garcia-Ocaña, A. Search for Related Content PubMed PubMed Citation Articles by Alonso, L. C. Articles by Garcia-Ocaña, A. Social Bookmarking                What's this?

Glucose infusion in mice: a new model to induce ß-cell replication

¹Division of Endocrinology, University of Pittsburgh Department of Medicine, Pittsburgh, PA 15261, USA
²Division of Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh Department of Medicine, Pittsburgh, PA 15261, USA
³Department of Developmental Biology, Stanford University, Stanford, CA 94305, USA
⁴Department of Medicine (Oncology Division), Stanford University, Stanford, CA 94305, USA

Correspondence: alonsol{at}dom.pitt.edu

Key Words: Glucose • pancreatic beta cell • proliferation • diabetes mellitus • mouse

Developing new techniques to induce beta cells to replicate is a major goal in diabetes research. Endogenous beta cells replicate in response to metabolic changes, such as obesity and pregnancy, which increase insulin requirement. Mouse genetic models promise to reveal the pathways responsible for compensatory beta cell replication. However, no simple, short term, physiologic replication stimulus exists to test mouse models for compensatory replication. Here we present a new tool to induce beta cell replication in living mice. Four day glucose infusion is well tolerated by mice as measured by hemodynamics, body weight, organ weight, food intake and corticosterone level. Mild sustained hyperglycemia and hyperinsulinemia induce a robust and significant five-fold increase in beta cell replication. Glucose-induced beta cell replication is dose- and time-dependent. Beta cell mass, islet number, beta cell size, and beta cell death are not altered by glucose infusion over this time frame. Glucose infusion increases both the total protein abundance and nuclear localization of cyclin D2 in islets, which has not been previously reported. Thus, we have developed a new model to study the regulation of compensatory beta cell replication, and we describe important novel characteristics of mouse beta cell responses to glucose in the living pancreas.

CiteULike

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				I. Cozar-Castellano, G. Harb, K. Selk, K. Takane, R. Vasavada, B. Sicari, B. Law, P. Zhang, D. K. Scott, N. Fiaschi-Taesch, et al. Lessons From the First Comprehensive Molecular Characterization of Cell Cycle Control in Rodent Insulinoma Cell Lines Diabetes, November 1, 2008; 57(11): 3056 - 3068. [Abstract] [Full Text] [PDF]

				A. El Ouaamari, N. Baroukh, G. A. Martens, P. Lebrun, D. Pipeleers, and E. van Obberghen miR-375 Targets 3'-Phosphoinositide-Dependent Protein Kinase-1 and Regulates Glucose-Induced Biological Responses in Pancreatic {beta}-Cells Diabetes, October 1, 2008; 57(10): 2708 - 2717. [Abstract] [Full Text] [PDF]

				D. K. Hagman, M. G. Latour, S. K. Chakrabarti, G. Fontes, J. Amyot, C. Tremblay, M. Semache, J. A. Lausier, V. Roskens, R. G. Mirmira, et al. Cyclical and Alternating Infusions of Glucose and Intralipid in Rats Inhibit Insulin Gene Expression and Pdx-1 Binding in Islets Diabetes, February 1, 2008; 57(2): 424 - 431. [Abstract] [Full Text] [PDF]