The glycosphingolipid sulfatide in the islets of Langerhans in rat pancreas is processed through recycling: possible involvement in insulin trafficking

In previous studies we have shown that sulfatide (galactosylceramide-3-O-su lfate), in various species, is present in the insulin-producing cells in pa ncreatic islets of Langerhans, In this study the synthesis of sulfatide in the islets has been investigated by pulse chase labeling at varying glucose levels and in the presence or absence of the glycosphingolipid synthesis i nhibitory agents, Brefeldin A, fumonisin B1 and chloroquine and the distrib ution of sulfatide by immune-electron microscopy, The data showed that (1) sulfatide was produced in islets of Langerhans, (2) the main pathway for sy nthesis was through recycling involving partial degradation in the lysosome , and that (3) high glucose levels, although not primarily reflected in an increased synthesis of sulfatide, lead to an increased expression of mRNA f or the UDP-galactose:ceramide galactosyltransferase, producing the immediat e precursor of sulfatide, Furthermore, mass spectrometry analyses revealed a high proportion of short chain fatty acids, C16:0 (50 %) and no hydroxyla ted forms and thus special physicochemical properties, indicating important differences between pancreatic and brain/neural sulfatide, Immune electron microscopy revealed an intracellular expression of sulfatide in the secret ory granules, the Golgi network and the lysosomes of the islets, These resu lts indicate that sulfatide follows the same intracellular route as insulin and suggest a functional association between these molecules. We have rais ed the hypothesis that sulfatide possibly plays a role in the tracfficking of insulin in the islets of Langerhans in rat pancreas.