Recovery of islet beta-cell function in streptozotocin- induced diabetic mice: an indirect role for the spleen.
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.
Yin
Dengping
D
Section of Transplantation, Department of Surgery, The University of Chicago, Chicago, IL 60637, USA.
Tao
Jing
J
Lee
David D
DD
Shen
Jikun
J
Hara
Manami
M
Lopez
James
J
Kuznetsov
Andrey
A
Philipson
Louis H
LH
Chong
Anita S
AS
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
D001786:Blood Glucose