Beta-cell function in mice injected with mononuclear splenocytes from multiple-dose streptozotocin diabetic mice.
Multiple low doses of streptozotocin (mid sz 40 mg/kg/day, five consecutive days) induce autoimmune diabetes in mice. The aim of the present work was to study beta-cell function in mice injected with splenocytes from mid-sz diabetic mice. Mononuclear splenocytes (MS) from control or diabetic donors were injected into syngeneic C57BL/6J healthy mice (5 x 10(7) MS, ip). MS from diabetic donors did not produce basal hyperglycemia, but they induced abnormal ip glucose tolerance in recipient mice. These "diabetic" MS were also preferentially trapped by the recipient's pancreas. Perifused pancreas from mice injected with MS from mid sz-diabetic donors showed a diminished first and second phase of glucose-induced insulin secretion after 15 days of the cell injection. At this time, pancreatic insulin content among MS recipients did not differ from that found in controls or diabetic donors. Diabetic MS treated with Mitomycin C prior to transfer did not inhibit insulin secretion in recipient mice. Injection of MS from mice made diabetic by a single high sz dose (200 mg/kg) did not induce any alterations of the insulin secretion in recipients. There is enough evidence when using athymic and euthymic (BALB/c nu/nu and +/nu) mice to suggest that proliferation of the injected splenocytes enhanced the progression to the diabetic state, and that both donor and recipient T lymphocytes played an important part in this progression. The results suggest that injection of MS from mid sz-diabetic mice interfere with glucose-stimulated insulin secretion in recipient mice and provide a basis for the study of the mechanisms involved in the onset and modulation of autoimmune pancreatic aggression.
Arata
M
M
Centro de Investigaciones Endocrinologicas (CEDIE), Hospital de Niños, Dr. R. Gutiérrez, Buenos Aires, Argentina.
Fabiano de Bruno
L
L
Goncalvez Volpini
W M
WM
Quintans
J C
JC
D'Alessandro
V G
VG
Braun
M
M
Basabe
J C
JC
D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology; D003921:Diabetes Mellitus, Experimental / Q000276:immunology*; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000503:physiopathology*; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D013154:Spleen / Q000166:cytology; D013311:Streptozocin; D013601:T-Lymphocytes / Q000276:immunology
D007328:Insulin; D013311:Streptozocin