       Document 0725
 DOCN  M9620725
 TI    Insulin-like growth factor-1 (IGF-1) protects NOD mice from insulitis
       and diabetes.
 DT    9602
 AU    Bergerot I; Fabien N; Maguer V; Thivolet C; INSERM U. 197, Faculte de
       Medecine, Alexis Carrel, Lyon,; France.
 SO    Clin Exp Immunol. 1995 Nov;102(2):335-40. Unique Identifier : AIDSLINE
       MED/96069884
 AB    To evaluate the effect of IGF-1 on the autoimmune process of beta cell
       destruction, permissive non-obese diabetic (NOD) recipients were
       adoptively transferred with 7 x 10(6) autoreactive T cells from diabetic
       NOD mice and were administered subcutaneously 10 micrograms rhIGF-1,
       twice daily for 3 weeks. Administration of rhIGF-1 reduced the final
       incidence of successful transfers of diabetes observed in only 6/24 mice
       (25%) versus 12/21 (57%) in control mice. A marked reduction of
       insulitis during histological analysis of pancreatic glands was also
       observed. Mice treated with rhIGF-1 had a higher percentage of intact
       islets (48.6 +/- 12% versus 1.6 +/- 1.1%, P = 0.001) and a lower
       percentage of infiltrated islets. Islets from rhIGF-1-treated mice had a
       more intense insulin staining reflecting a higher beta cell mass, but no
       difference was observed in the amount of insulin content of pancreatic
       extracts and in the amounts of mRNA transcripts for proinsulin. No
       difference was also observed in the titres of three islet cell antibody
       (ICA)-positive sera and in the pattern of A2B5 staining. Some mice
       developed diabetes and severe islet cell infiltration despite rhIGF-1,
       thus indicating that some committed T cells were still able to invade
       the islets and cause beta cell destruction. The percentages of CD4+ and
       CD8+ T cells in the spleen of experimental mice were similar. To
       evaluate the effects of rhIGF-1 on cell trafficking in recipient mice, T
       cells from diabetic NOD Thy-1,2 mice injected into congenic NOD-N
       Thy-1,1 mice were monitored 3 weeks after adoptive cell transfer. The
       percentage of Thy-1,2+ T cells was significantly reduced in the spleen
       (10.8 +/- 1.3% versus 17.2 +/- 3.9%, P = 0.004) of rhIGF-1 treated mice
       in contrast to the thymus (68.4 +/- 7.9% versus 72.87 +/- 6.2%, P =
       0.306), suggesting that rhIGF-1 could influence T cell trafficking to
       the lymphoid organs. The findings that rhIGF-1 has protective effects in
       autoimmune diabetes opens new perspectives for future experiments as
       well as for preventive strategies in human type I diabetes.
 DE    Animal  CD4-Positive T-Lymphocytes/IMMUNOLOGY  CD8-Positive
       T-Lymphocytes/IMMUNOLOGY  Diabetes Mellitus,
       Insulin-Dependent/IMMUNOLOGY/*PREVENTION &  CONTROL  Female  Immunity,
       Cellular  Immunization, Passive  Insulin-Like Growth Factor
       I/*THERAPEUTIC USE  Islets of Langerhans/IMMUNOLOGY  Male  Mice  Mice,
       Inbred NOD  Recombinant Proteins  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

