This study investigates the uptake and distribution of sulfatide, a glycosphingolipid, in the gastrointestinal tract and pancreas of mice. Sulfatide, found in various mammalian tissues, has been shown to play a role in insulin processing and secretion in pancreatic beta cells. The study examined the uptake of exogenously administered sulfatide in mice, both orally and via intraperitoneal (i.p.) injection, and its distribution to the pancreas and islets of Langerhans. Oral administration of radioactive sulfatide resulted in its uptake in the gastrointestinal tract, with selective uptake of short-chain and/or hydroxylated sulfate fatty acid isoforms in the small intestine. However, sulfatide was not detected in the pancreas after oral administration. In contrast, i.p. administration of radioactive sulfatide led to its uptake in the pancreas, with the C16:0 isoform being particularly significant. In vitro studies using isolated rat islets showed that sulfatide was endocytosed and metabolized by pancreatic islets, regardless of its fatty acid length. The study also found that sulfatide was degraded in the gastrointestinal tract within 24 hours, suggesting that it may be rapidly processed or removed. However, the presence of sulfatide in the pancreas after i.p. administration indicated that it could be taken up and retained in this organ. The results suggest that sulfatide may have a role in beta cell function and could be relevant to the pathogenesis of both type 1 and type 2 diabetes. The study highlights the potential of sulfatide as a target for further research in diabetes and related conditions.This study investigates the uptake and distribution of sulfatide, a glycosphingolipid, in the gastrointestinal tract and pancreas of mice. Sulfatide, found in various mammalian tissues, has been shown to play a role in insulin processing and secretion in pancreatic beta cells. The study examined the uptake of exogenously administered sulfatide in mice, both orally and via intraperitoneal (i.p.) injection, and its distribution to the pancreas and islets of Langerhans. Oral administration of radioactive sulfatide resulted in its uptake in the gastrointestinal tract, with selective uptake of short-chain and/or hydroxylated sulfate fatty acid isoforms in the small intestine. However, sulfatide was not detected in the pancreas after oral administration. In contrast, i.p. administration of radioactive sulfatide led to its uptake in the pancreas, with the C16:0 isoform being particularly significant. In vitro studies using isolated rat islets showed that sulfatide was endocytosed and metabolized by pancreatic islets, regardless of its fatty acid length. The study also found that sulfatide was degraded in the gastrointestinal tract within 24 hours, suggesting that it may be rapidly processed or removed. However, the presence of sulfatide in the pancreas after i.p. administration indicated that it could be taken up and retained in this organ. The results suggest that sulfatide may have a role in beta cell function and could be relevant to the pathogenesis of both type 1 and type 2 diabetes. The study highlights the potential of sulfatide as a target for further research in diabetes and related conditions.