Horm Metab Res 2005; 37(2): 63-67
DOI: 10.1055/s-2005-861155
Original Basic
© Georg Thieme Verlag KG Stuttgart · New York

Transfer of Diabetes from Prediabetic NOD Mice to NOD-SCID/SCID Mice: Association with Pancreatic Insulin Content

M.  Füchtenbusch1, 2 , E.  Larger1 , K.  Thebault1 , C.  Boitard1
  • 1INSERM U561, Hopital Saint-Vincent-de-Paul, Paris, France
  • 2Hospital München-Schwabing, 3rd Medical Department, Diabetes Research Institute, Munich, Germany
Further Information

Publication History

Received 8 April 2004

Accepted after revision 5 August 2004

Publication Date:
21 March 2005 (online)

Abstract

Splenocytes from prediabetic female NOD mice can transfer diabetes to NOD-SCID mice. Whereas the kinetics of disease transfer was shown to be a function of the age of donor splenocytes, information is scarce as to how the stage of autoimmune disease, as evaluated by pancreatic insulin content, is related to the diabetogenic potency of splenic T-cells. We therefore determined individual diabetes transfer times after an i. v. injection of splenocytes from prediabetic NOD mice of different ages into female NOD-SCID mice in relation to the diabetes incidence in NOD donor mice and their pancreatic insulin contents. Three groups (n = 8) of NOD mice aged 5, 11, and 17 weeks (wk) underwent splenectomy and hemipancreatectomy. After that, 10×106 splenocytes either pooled from all donor NOD mice of the different age groups or individually from single donor mice were transferred to groups of four 6-week-old NOD-SCID mice, respectively, in two sets of experiments. Insulin was extracted from the resected hemipancreas, and the insulin content was determined by a RIA. Diabetes in the NOD-SCID cohort occurred after a mean time of 126 days after transfer of pooled splenocytes from 5-week-old NODs, after 68 days (transfer from 11-week-old NODs), and after a mean time of 43 days (transfer from 17-week-old NODs, 5 vs. 11 wk: p < 0.02, 11 vs. 17 wk: p < 0.001). Individual time to diabetes positively correlated with diabetes transfer times in NOD-SCID recipients (p < 0.0001) in the 17-week-old NOD mice, confirming previous diabetes transfer studies in hemi-pancreatectomized NOD mice. Furthermore, individual insulin concentrations in 17-week-old NOD mice also positively correlated to diabetes transfer times in recipient mice (p < 0.0001). No such correlations for these parameters were seen for the 5 and 11-week-old NOD mice (time to diabetes: 11 wk, p = 0.14, 5 wk, p = 0.75; insulin content: 11 wk, p = 0.81, 5 wk, p = 0.14). These data suggest that destructive T-cell activity increases during the course of islet autoimmunity. The immune response seems to be programmed for β-cell destruction just before diabetes onset. This is the only time that pancreatic insulin content predicts the impending onset of diabetes.

References

PD Dr. Martin Füchtenbusch

Diabetes Research Institute, 3rd Medical Department, Academic Hospital München Schwabing

Kölner Platz 1 · 80804 München · Germany

Phone: +49 (89) 30 79 31 14 ·

Fax: +49 (89) 308 17 33

Email: martin.fuechtenbusch@lrz.uni-muenchen.de