Repopulation of the atrophied thymus in diabetic rats by insulin-like growth factor I.
Atrophy of the thymus is one of the consequences of severe insulin deficiency. We describe here that the weight and the architecture of the thymus of diabetic rats is restored towards normal not only by insulin but also by insulin-like growth factor I (IGF-I) treatment. In contrast to insulin, this effect of IGF-I occurs despite persisting hyperglycemia and adrenal hyperplasia. We also investigated the in vivo effect of IGF-I on replication and differentiation of thymocytes from streptozotocin-induced diabetic rats. Thymocytes from diabetic rats incorporated less [3H]thymidine than did thymocytes from healthy rats. Insulin, as well as IGF-I treatment of diabetic rats increased [3H]thymidine incorporation by thymocytes. Flow cytometry of thymocytes labeled with monoclonal antibodies revealed a decreased expression of the Thy-1 antigen in diabetic rats compared with control rats. In addition, a major deficiency of thymocytes expressing simultaneously the W3/25 and the Ox8 antigens (corresponding to immature human CD4+/CD8+ thymocytes) was observed. These changes were restored towards normal by insulin as well as by IGF-I treatment. The antibody response to a T cell-dependent antigen (bovine serum albumin) was comparable in normal and diabetic rats. We conclude that IGF-I has important effects on the thymocyte number and the presence of CD4+/CD8+ immature cells in the thymus of diabetic rats despite persisting hyperglycemia. However, helper T-cell function for antibody production appears to be preserved even in the severely diabetic state.
Department of Medicine, University Hospital, Zürich, Switzerland.
K
K
Binz
P
P
Joller
P
P
Froesch
H
H
Binz
J
J
Zapf
E R
ER
Froesch
D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis*; D001284:Atrophy; D004261:DNA Replication / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000473:pathology*; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D007328:Insulin / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D051381:Rats; D011994:Recombinant Proteins / Q000097:blood / Q000494:pharmacology; D012016:Reference Values; D013002:Somatomedins / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D013950:Thymus Gland / Q000187:drug effects / Q000276:immunology / Q000473:pathology*
D000945:Antigens, Differentiation, T-Lymphocyte; D007328:Insulin; D011994:Recombinant Proteins; D013002:Somatomedins; D007334:Insulin-Like Growth Factor I