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This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: 297/3/E793    most recent 90878.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Piquer, S. Articles by Gomis, R. PubMed PubMed Citation Articles by Piquer, S. Articles by Gomis, R.

Role of iduronate-2-sulfatase in glucose-stimulated insulin secretion by activation of exocytosis

¹Endocrinology and Diabetes Unit, Laboratory of Diabetes and Obesity, Institut d'Investigacions Biomediques August Pi i Sunyer-Fundació Clínic, Hospital Clínic, Barcelona; ²Centro de Investigación Biomedica en Red de Diabetes y Enfermedades Metabólicas, Spain; and ³Instituto de Bioingeniería, Universidad Miguel Hernández, Elche, Spain

Submitted 28 October 2008 ; accepted in final form 3 July 2009

Iduronate-2-sulfatase (IDS) is a lysosomal enzyme expressed in pancreatic islets responsible for the degradation of proteoglycans such as perlecan and dermatan sulfate. Previous findings of our group demonstrated the involvement of IDS in the normal pathway of lysosomal degradation of secretory peptides, suggesting a role of this enzyme in β-cell secretory functionality. The present study was undertaken to characterize the effect of IDS overexpression on insulin release. INS1E cells were transiently transfected with a construct encoding human IDS (hIDS). hIDS overexpression was associated with a gain of function detected by a reduction in heparan sulfate content. hIDS potentiated the glucose-stimulated insulin secretory response compared with controls (61%) with no changes in insulin mRNA levels or insulin peptide content. Results on quantification of the exocytotic process showed a significant increase in hIDS-transfected cells compared with controls. Furthermore, ultramorphological analysis demonstrated an increase in the number of granules in the immediate vicinity of the plasma membrane in hIDS-transfected cells and a decrease in total vesicles per square micrometer. hIDS overexpression induced phosphorylation of protein kinase C (PKC) and its newly myristoylated alanine-rich C kinase substrate, MARCKS. We conclude that IDS has a role in glucose-stimulated insulin secretion via a mechanism that involves the activation of exocytosis through phosphorylation of PKC and MARCKS.

exocytosis; insulin secretion; lysosome; phosphorylation; β-cell