The lysosomal enzyme iduronate -2-sulfatase (IDS) is expressed in pancreatic islets and is responsible for degradation of proteoglycans such as perlecan and dermatan sulfate. To determine the role of Ids in islets, the expression and regulation of the gene and localization of the enzime were investigated in mouse pancreatic islets and clonal cells. The Ids gene was expressed in mouse islets, beta and alpha clonal cells, being localized intracellularly in lysosomes. The transcriptional expression of Ids in mouse islets increased with glucose in a dose-dependent manner (11.5 % at 5.5 mM; 40.2 % at 11.1 mM; 88 % at 16.7 mM* and 179 % at 24.4 mM*; * p<0.01 compared to secretion at 3mM glucose). This increase was not produced by glyceraldehyde (1 mM) or 6- deoxyglucose (21.4 mM) and blocked by the addition of mannoheptulose (21.4 mM). Neither insulin content nor secretory response to glucose (16.7 mM) was altered in mouse islets infected with lentiviral constructs carrying the IDS gene in sense orientation. Furthermore, no islet cell viability decrease was observed in mouse islets carrying lentiviral contracts compared to the controls. However, insulin content was reduced (35 % versus controls, p<0.001) in islets infected with IDS antisense construct, whilst the secretory response to glucose of those islets was maintained. Inhibition of IDS by antisense infection lead to an increase lysosomal size and a high rate of insulin granules degradation via the crinophagic rute in pancreatic beta cells. We conclude that IDS is localized in lysosomes in pancreatic islet cells and expression is regulated by glucose. IDS has a potential role in normal pathway of lysosomal degrada tion of secretory peptides and is likely to be essential to maintain pancreatic beta-cell function.