Arata M, Fabiano de Bruno L, Goncalvez Volpini W M, Quintans J C, D'Alessandro V G, Braun M, Basabe J C
Centro de Investigaciones Endocrinologicas (CEDIE), Hospital de Niños, Dr. R. Gutiérrez, Buenos Aires, Argentina.
Proc Soc Exp Biol Med. 1994 May;206(1):76-82. doi: 10.3181/00379727-206-43725.
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.
多次低剂量链脲佐菌素（中剂量40毫克/千克/天，连续五天）可诱导小鼠发生自身免疫性糖尿病。本研究的目的是研究注射中剂量链脲佐菌素诱导糖尿病小鼠的脾细胞后小鼠β细胞的功能。将来自对照或糖尿病供体的单核脾细胞（MS）注射到同基因C57BL/6J健康小鼠体内（5×10⁷个MS，腹腔注射）。来自糖尿病供体的MS不会导致基础血糖升高，但会诱导受体小鼠腹腔内葡萄糖耐量异常。这些“糖尿病”MS也优先被受体小鼠的胰腺捕获。注射来自中剂量链脲佐菌素诱导糖尿病供体的MS的小鼠，其胰腺在细胞注射15天后，葡萄糖诱导的胰岛素分泌的第一和第二阶段减少。此时，接受MS注射的小鼠胰腺胰岛素含量与对照组或糖尿病供体的小鼠无异。转移前用丝裂霉素C处理的糖尿病MS不会抑制受体小鼠的胰岛素分泌。注射单次高剂量链脲佐菌素（200毫克/千克）诱导糖尿病小鼠的MS，不会引起受体小鼠胰岛素分泌的任何改变。有足够的证据表明，使用无胸腺和有胸腺（BALB/c裸鼠和+/裸鼠）小鼠时，注射的脾细胞增殖会加速糖尿病状态的发展，并且供体和受体T淋巴细胞在这一过程中都起重要作用。结果表明，注射来自中剂量链脲佐菌素诱导糖尿病小鼠的MS会干扰受体小鼠葡萄糖刺激的胰岛素分泌，并为研究自身免疫性胰腺攻击的发生和调节机制提供了依据。
