Blomqvist Maria, Osterbye Thomas, Månsson Jan-Eric, Horn Thomas, Buschard Karsten, Fredman Pam
Institute of Clinical Neuroscience, Experimental Neuroscience Section, The Sahlgrenska Academy at Göteborg University, Sahlgrenska University Hospital/Mölndal, Sweden.
APMIS. 2003 Sep;111(9):867-77. doi: 10.1034/j.1600-0463.2003.1110905.x.
Sulfatide (3'-sulfogalactosyl-ceramide) is a glycosphingolipid mainly located in the nervous system, but has also been found in the islets of Langerhans. Previous studies have suggested that sulfatide is involved in insulin processing and secretion. In this study, sulfatide expression and metabolism in pancreas and isolated islets of the type II diabetes models, ob/ob- and db/db mouse, was investigated using TLC-ELISA, metabolic labelling and electron microscopy. As in non-diabetic Lewis rat and human pancreas, sulfatide was located in secretory granules of the beta cells. However, the type II diabetic animal models and their background strains had an altered sulfatide expression, involving the lack of the C16:0 sulfatide fatty acid isoform, compared to non-diabetic Lewis rat, BALB/c mouse and human pancreatic tissue, in which the two dominating pancreatic sulfatide isoforms C16:0 and C24:0 are expressed. Correspondingly, in isolated ob/ob islets, sulfatide synthesis excluded the production of C16:0 sulfatide. Insulin administration to ob/ob mouse, which lowers beta cell activity, resulted in significantly increased sulfatide expression in pancreas (p=0.0003), but still no expression of the C16:0 sulfatide isoform. In vitro, the C16:0 sulfatide was shown to be the isomer involved in the preservation of insulin crystals. Thus, it is hypothesized that the selection of sulfatide isomers in pancreas might be a genetic factor contributing to disease development in type II diabetic animal models.
硫苷脂(3'-硫酸半乳糖神经酰胺)是一种主要存在于神经系统中的糖鞘脂,但也在胰岛中被发现。先前的研究表明硫苷脂参与胰岛素的加工和分泌。在本研究中,使用薄层层析-酶联免疫吸附测定法、代谢标记法和电子显微镜,对II型糖尿病模型ob/ob和db/db小鼠的胰腺和分离的胰岛中的硫苷脂表达和代谢进行了研究。与非糖尿病的Lewis大鼠和人类胰腺一样,硫苷脂位于β细胞的分泌颗粒中。然而,与非糖尿病的Lewis大鼠、BALB/c小鼠和人类胰腺组织相比,II型糖尿病动物模型及其背景品系的硫苷脂表达发生了改变,其中缺乏C16:0硫苷脂脂肪酸异构体,而在非糖尿病的Lewis大鼠、BALB/c小鼠和人类胰腺组织中表达两种主要的胰腺硫苷脂异构体C16:0和C24:0。相应地,在分离的ob/ob胰岛中,硫苷脂的合成不包括C16:0硫苷脂的产生。给ob/ob小鼠注射胰岛素会降低β细胞活性,导致胰腺中硫苷脂表达显著增加(p=0.0003),但仍然没有C16:0硫苷脂异构体的表达。在体外,C16:0硫苷脂被证明是参与胰岛素晶体保存的异构体。因此,据推测胰腺中硫苷脂异构体的选择可能是导致II型糖尿病动物模型疾病发展的一个遗传因素。