Syndecan-4 is associated with beta-cells in the pancreas and the MIN6 beta-cell line.

Basement membranes (BM) in the pancreatic islet are important for islet survival and function, but supplementation of isolated islets with these components have had limited success. Currently, little is understood about which BM components and proteoglycans are essential to maintaining islet homeostasis. This study therefore aimed to characterize the BM components and proteoglycans of the islet in the mouse, rat and rabbit species. The BM of the mouse islet was varied in continuity around the islet and was discontinuous in the rat and rabbit islets. The BM consisted of collagen IV, laminin, fibronectin and perlecan in the mouse and was in tight association with the underlying islet endothelium. None of these components were found directly associated with the ß-cells in tissue and in the MIN6 ß-cell line. In contrast, heparan sulfate (HS) was distributed throughout the islet in all three species in a pattern distinctly different to that of perlecan and was observed mainly on the ß-cells and not the α-cells in the mouse and rat. Similarly, syndecan-4 showed a staining pattern almost identical to that of HS and was mostly observed on the ß-cells, not α-cells, in the mouse and rat. Both HS and syndecan-4 were also observed in the MIN6 ß-cell line. The mouse islet and MIN6 syndecan-4 were both ~37 kDa in size, after deglycosylation with heparitinase. These results indicate that syndecan-4 may play an important role in ß-cell function and that the cell-surface HS proteoglycans may be the missing link to maintaining islet longevity after isolation.

Matrix components and scaffolds for sustained islet function.

The clinical treatment of diabetes by islet transplantation is limited by low islet survival rates. A fundamental reason for this inefficiency is likely due to the removal of islets from their native environment. The isolation process not only disrupts interactions between blood vessels and endocrine cells, but also dramatically changes islet cell interaction with the extracellular matrix (ECM). Biomolecular cues from the ECM are important for islet survival, proliferation, and function; however, very little is known about the composition of islet ECM and the role each component plays. Without a thorough understanding of islet ECM, current endeavors to prolong islet survival via scaffold engineering lack a systematic basis. The following article reviews current knowledge of islet ECM and attempts to explain the roles they play in islet function. In addition, the effects of in vitro simulations of the native islet scaffold will be evaluated. Greater understanding in these areas will provide a preliminary platform from which a sustainable bioartificial pancreas may be developed.