Recovery of islet β-cell function in streptozotocin-induced diabetic mice: An indirect role for the spleen

Dengping Yin, Jing Tao, David D. Lee, Jikun Shen, Manami Hara, James Lopez, Andrey Kuznetsov, Louis H. Philipson, Anita S. Chong

Research output: Contribution to journalArticle

65 Scopus citations

Abstract

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

Original languageEnglish (US)
Pages (from-to)3256-3263
Number of pages8
JournalDiabetes
Volume55
Issue number12
DOIs
StatePublished - Dec 1 2006

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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    Yin, D., Tao, J., Lee, D. D., Shen, J., Hara, M., Lopez, J., Kuznetsov, A., Philipson, L. H., & Chong, A. S. (2006). Recovery of islet β-cell function in streptozotocin-induced diabetic mice: An indirect role for the spleen. Diabetes, 55(12), 3256-3263. https://doi.org/10.2337/db05-1275