Ziegler M, Teneberg S, Witt S, Ziegler B, Hehmke B, Kohnert K D, Egeberg J, Karlsson K A, Lernmark A
Hagedorn Research Laboratory, Gentofte, Denmark.
J Immunol. 1988 Jun 15;140(12):4144-50.
Diabetes was induced in BALB/c mice by four injections of a subdiabetogenic dose (40 mg/kg) of streptozotocin in combination with CFA. The treatment increased the plasma glucose from 5.8 +/- 0.1 to 22.1 +/- 1.3 mmol/liter (n = 9). The diabetic animals had circulating islet cell surface antibodies (75%), and a monoclonal islet cell surface IgM antibody, K56aF3, generated from one of the diabetic BALB/c mice, mediated C-Dependent cytotoxicity against insulin-producing cells and inhibited glucose-stimulated insulin release from isolated rat islets. Solid phase assay on thin layer chromatograms showed no binding of the K56aF3 antibody to glycolipids prepared from relevant cells. However, testing against a series of glycolipids of various non-pancreatic origins showed a preferential binding to a nine-sugar glycolipid isolated from human erythrocytes carrying an unusual blood group A determinant (type 3). It is suggested that this mAb may be associated with the development of diabetes following a combination of polyclonal activation and non-diabetogenic doses of streptozotocin.
通过四次注射亚致糖尿病剂量（40毫克/千克）的链脲佐菌素并结合完全弗氏佐剂（CFA），在BALB/c小鼠中诱导糖尿病。该治疗使血浆葡萄糖水平从5.8±0.1毫摩尔/升升高至22.1±1.3毫摩尔/升（n = 9）。糖尿病动物存在循环胰岛细胞表面抗体（75%），并且从一只糖尿病BALB/c小鼠产生的单克隆胰岛细胞表面IgM抗体K56aF3介导了对胰岛素产生细胞的补体依赖性细胞毒性，并抑制了从分离的大鼠胰岛中葡萄糖刺激的胰岛素释放。薄层色谱图上的固相分析表明，K56aF3抗体与从相关细胞制备的糖脂没有结合。然而，针对一系列各种非胰腺来源的糖脂进行检测时，发现该抗体优先结合从携带异常A血型决定簇（3型）的人红细胞中分离出的一种九糖糖脂。有人提出，这种单克隆抗体可能与多克隆激活和非致糖尿病剂量的链脲佐菌素联合作用后糖尿病的发生有关。
