Cresto Juan C, Fabiano de Bruno Lidia E, Cao Gabriel F, Pastorale Claudia F, Confalonieri Nicolas, del Carmen Camberos María, Basabe Juan C
Centro de Investigaciones Endocrinológicas (CEDIE-CONICET), Htal. de Niños R. Gutierrez, Buenos Aires, Argentina.
Pancreas. 2006 Nov;33(4):403-11. doi: 10.1097/01.mpa.0000236740.07854.b1.
We studied the effect of acetyl-l-carnitine plus nicotinamide (AC + N) on murine diabetes mellitus induced by multiple low doses of streptozotocin.
Male C57BL/6J inbred mice were injected intraperitoneally with citrate buffer or streptozotocin (40 mg/kg) for 5 consecutive days, followed by injections of saline solution or AC + N (50 + 25 mg/kg) from days 6 to 110. Four groups were studied: normal control mice (C), treated normal control mice (TC), diabetic mice (D), and treated diabetic mice (TD). TD group was divided into 2 at day 86; treatment was suspended in one group (TDs) and continued in the other until day 110.
Weight, plasma glucose, plasma insulin, cellular immune aggression, glucose-stimulated insulin secretion from perifused pancreatic slices, and pancreas histology were studied in each experimental group. Diabetic mice treated with AC + N showed improvements in weight, plasma glucose, and plasma insulin levels without mortality, reaching control values at day 110. Cellular immune aggression and insulin release from pancreatic slices perfusions improved without reaching control values. Histology showed that insulin-immunostained area, the index of insulin immunostained beta cells and beta-cell size, was normalized at the end of the study.
The treatment with AC + N induced remission of autoimmune type 1 diabetes in mice produced by multiple low doses of streptozotocin.
我们研究了乙酰左旋肉碱加烟酰胺(AC + N)对多次低剂量链脲佐菌素诱导的小鼠糖尿病的影响。
雄性C57BL/6J近交系小鼠连续5天腹腔注射柠檬酸盐缓冲液或链脲佐菌素(40 mg/kg),随后从第6天至第110天注射生理盐水或AC + N(50 + 25 mg/kg)。研究了四组:正常对照小鼠(C)、经处理的正常对照小鼠(TC)、糖尿病小鼠(D)和经处理的糖尿病小鼠(TD)。TD组在第86天分为两组;一组暂停治疗(TDs),另一组继续治疗直至第110天。
对每个实验组的体重、血浆葡萄糖、血浆胰岛素、细胞免疫攻击、灌注胰腺切片的葡萄糖刺激胰岛素分泌和胰腺组织学进行了研究。用AC + N治疗的糖尿病小鼠体重、血浆葡萄糖和血浆胰岛素水平有所改善,且无死亡,在第110天达到对照值。细胞免疫攻击和胰腺切片灌注的胰岛素释放有所改善,但未达到对照值。组织学显示,在研究结束时,胰岛素免疫染色面积、胰岛素免疫染色β细胞指数和β细胞大小恢复正常。
AC + N治疗可使多次低剂量链脲佐菌素诱导的小鼠自身免疫性1型糖尿病得到缓解。