Title | Glucose infusion in mice: a new model to induce beta-cell replication. |
Publication Type | Journal Article |
Year of Publication | 2007 |
Authors | Alonso LC, Yokoe T, Zhang P, Scott DK, Kim SK, O'Donnell CP, Garcia-OcaƱa A |
Journal | Diabetes |
Volume | 56 |
Issue | 7 |
Pagination | 1792-801 |
Date Published | 2007 Jul |
ISSN | 1939-327X |
Keywords | Animals, Cell Proliferation, Cyclin D2, Cyclins, Dose-Response Relationship, Drug, Glucose, Infusions, Intravenous, Insulin-Secreting Cells, Male, Mice, Models, Animal |
Abstract | 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, physiological 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 fivefold 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. |
DOI | 10.2337/db06-1513 |
Alternate Journal | Diabetes |
PubMed ID | 17400928 |
PubMed Central ID | PMC2921922 |
Grant List | DK-076562 / DK / NIDDK NIH HHS / United States DK067351 / DK / NIDDK NIH HHS / United States K08 DK076562 / DK / NIDDK NIH HHS / United States R01 DK067351-04 / DK / NIDDK NIH HHS / United States R01 DK067351 / DK / NIDDK NIH HHS / United States K08 DK076562-01 / DK / NIDDK NIH HHS / United States |