title: Glucose infusion in mice: a new model to induce beta-cell replication.
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.
authors.affiliation: University of Pittsburgh, Division of Endocrinology, 200 Lothrop St., BST E1140, Pittsburgh, PA 15261, USA. alonsol@dom.pitt.edu
authors.forename: Laura C
authors.initials: LC
authors.lastname: Alonso
authors.forename: Takuya
authors.initials: T
authors.lastname: Yokoe
authors.forename: Pili
authors.initials: P
authors.lastname: Zhang
authors.forename: Donald K
authors.initials: DK
authors.lastname: Scott
authors.forename: Seung K
authors.initials: SK
authors.lastname: Kim
authors.forename: Christopher P
authors.initials: CP
authors.lastname: O'Donnell
authors.forename: Adolfo
authors.initials: A
authors.lastname: Garcia-Ocaña
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D056742:Cyclin D2; D016213:Cyclins / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000494:pharmacology*; D007262:Infusions, Intravenous; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D023421:Models, Animal
chemical_list: C486196:Ccnd2 protein, mouse; D056742:Cyclin D2; D016213:Cyclins; D005947:Glucose