Effects of heparan sulfate proteoglycan syndecan-4 on the insulin secretory response in a mouse pancreatic β-cell line, MIN6.

Heparan sulfate proteoglycans (HSPGs) comprise a core protein to which extracellular glycosaminoglycan chains are attached. Syndecan-4, one of the major HS-containing core proteins, is distributed on the cell surface, where they interact with various protein ligands and regulate a wide range of biological activities. Here, we propose that the core protein of HSPGs is involved in the insulin secretory response. To investigate the participation of HSPGs in the insulin-secretion mechanism, MIN6 cells, a mouse pancreatic β-cell line, were subcloned. The subcloned MIN6 cells were selected based on their insulin secretory response, the expression of HS and core proteins. The results from these screening experiments indicated that only syndecan-4-expressing subclones are able to secrete insulin in response to glucose. Silencing of syndecan-4 reduced glucose-induced insulin secretion, whereas the overexpression of syndecan-4 increased the insulin secretory response. These data indicate that the HSPG syndecan-4 plays important role(s) in the insulin secretory response.