Sulfatide controls insulin secretion by modulation of ATP-sensitive K+-channel activity and Ca2+-dependent exocytosis in rat pancreatic β-cells
Sulfatide controls insulin secretion by modulation of ATP-sensitive K+-channel activity and Ca2+-dependent exocytosis in rat pancreatic β-cells
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DOI：
10.2337/diabetes.51.8.2514
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发表时间：
2002-08-01
期刊：
影响因子：
7.7
通讯作者：
Gromada, J
中科院分区：
文献类型：
--
作者：
Buschard, K;Hoy, M;Gromada, J
鞘糖脂硫酸脂存在于分泌颗粒和胰腺β细胞表面，并且在大多数新诊断的1型糖尿病患者的血清中发现抗硫酸脂抗体（阿萨; IgG 1）。在这里，我们证明，硫苷脂产生的葡萄糖和浓度依赖性抑制胰岛素释放从离体大鼠胰岛。这种胰岛素分泌的抑制是由于单个大鼠β细胞中ATP敏感性K+-（K-ATP）通道的激活。未观察到硫苷脂对全细胞Ca 2+通道活性或葡萄糖诱导的细胞质Ca 2+浓度升高的影响。有趣的是，硫苷脂刺激Ca 2+依赖性胞吐测定电容测量和去极化诱导的胰岛素分泌暴露于二氮嗪和高外部KCl的胰岛。单克隆硫苷脂抗体Sulph I以及ASA阳性血清通过抑制Ca 2+依赖性胞吐作用减少2葡萄糖诱导的胰岛素分泌。我们的数据表明，硫苷脂是重要的葡萄糖诱导的胰岛素分泌的控制和增加和减少的硫苷脂含量有影响的分泌能力的个别β细胞。
The glycosphingolipid sulfatide is present in secretory granules and at the surface of pancreatic beta-cells, and antisulfatide antibodies (ASA; IgG1) are found in serum from the majority of patients with newly diagnosed type 1 diabetes. Here we demonstrate that sulfatide produced a glucose- and concentration-dependent inhibition of insulin release from isolated rat pancreatic islets. This inhibition of insulin secretion was due to activation of ATP-sensitive K+-(K-ATP) channels in single rat beta-cells. No effect of sulfatide was observed on whole-cell Ca2+-channel activity or glucose-induced elevation of cytoplasmic Ca2+ concentration. It is interesting that sulfatide stimulated Ca2+-dependent exocytosis determined by capacitance measurements and depolarized-induced insulin secretion from islets exposed to diazoxide and high external KCl. The monoclonal sulfatide antibody Sulph I as well as ASA-positive serum reduced 2 glucose-induced insulin secretion by inhibition of Ca2+-dependent exocytosis. Our data suggest that sulfatide is important for the control of glucose-induced insulin secretion and that both an increase and a decrease in the sulfatide content have an impact on the secretory capacity of the individual beta-cells.