title: Recovery of islet beta-cell function in streptozotocin- induced diabetic mice: an indirect role for the spleen.
abstract: Limitations in islet beta-cell transplantation as a therapeutic option for type 1 diabetes have prompted renewed interest in islet regeneration as a source of new islets. In this study we tested whether severely diabetic adult C57BL/6 mice can regenerate beta-cells. Diabetes was induced in C57BL/6 mice with high-dose streptozotocin (160-170 mg/kg). In the absence of islet transplantation, all diabetic mice remained diabetic (blood glucose >400 mg/dl), and no spontaneous reversal of diabetes was observed. When syngeneic islets (200/mouse) were transplanted into these diabetic mice under a single kidney capsule, stable restoration of euglycemia for >/=120 days was achieved. Removal of the kidney bearing the transplanted islets at 120 days posttransplantation revealed significant restoration of endogenous beta-cell function. This restoration of islet function was associated with increased beta-cell mass, as well as beta-cell hypertrophy and proliferation. The restoration of islet cell function was facilitated by the presence of a spleen; however, the facilitation was not due to the direct differentiation of spleen-derived cells into beta-cells. This study supports the possibility of restoring beta-cell function in diabetic individuals and points to a role for the spleen in facilitating this process.
authors.affiliation: Section of Transplantation, Department of Surgery, The University of Chicago, Chicago, IL 60637, USA.
authors.forename: Dengping
authors.initials: D
authors.lastname: Yin
authors.forename: Jing
authors.initials: J
authors.lastname: Tao
authors.forename: David D
authors.initials: DD
authors.lastname: Lee
authors.forename: Jikun
authors.initials: J
authors.lastname: Shen
authors.forename: Manami
authors.initials: M
authors.lastname: Hara
authors.forename: James
authors.initials: J
authors.lastname: Lopez
authors.forename: Andrey
authors.initials: A
authors.lastname: Kuznetsov
authors.forename: Louis H
authors.initials: LH
authors.lastname: Philipson
authors.forename: Anita S
authors.initials: AS
authors.lastname: Chong
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002454:Cell Differentiation; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000473:pathology / Q000503:physiopathology*; D005951:Glucose Tolerance Test; D050417:Insulin-Secreting Cells / Q000473:pathology / Q000502:physiology*; D007700:Kinetics; D051379:Mice; D008810:Mice, Inbred C57BL; D012016:Reference Values; D013154:Spleen / Q000503:physiopathology*; D013997:Time Factors
chemical_list: D001786:Blood Glucose