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Diabetes 55:3256-3263, 2006
DOI: 10.2337/db05-1275
© 2006 by the American Diabetes Association
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Recovery of Islet ß-Cell Function in Streptozotocin- Induced Diabetic Mice

An Indirect Role for the Spleen

Dengping Yin1, Jing Tao1, David D. Lee1, Jikun Shen1, Manami Hara2, James Lopez2, Andrey Kuznetsov2, Louis H. Philipson2, and Anita S. Chong1

1 Section of Transplantation, Department of Surgery, The University of Chicago, Chicago, Illinois
2 Section of Endocrinology, Department of Medicine, The University of Chicago, Chicago, Illinois

Address correspondence and reprint requests to Anita S. Chong, PhD, Section of Transplantation, Department of Surgery, The University of Chicago, Chicago, IL 60637. Tel: 773–702 5521; FAX: 773-702-5517; E-mail: achong{at}uchicago.edu

Abbreviations: [Ca2+]i, intracellular calcium contration; FISH, fluorescence in situ hybridization; FITC, fluoroscein isothiocyanate; IPGTT, intraperitoneal glucose tolerance test; STZ, streptozotocin

Limitations in islet ß-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 ß-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 ß-cell function. This restoration of islet function was associated with increased ß-cell mass, as well as ß-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 ß-cells. This study supports the possibility of restoring ß-cell function in diabetic individuals and points to a role for the spleen in facilitating this process.


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Copyright © 2006 by the American Diabetes Association.