| First Author | Matsuzawa T | Year | 2018 |
| Journal | Biochem Biophys Res Commun | Volume | 499 |
| Issue | 3 | Pages | 688-695 |
| PubMed ID | 29605295 | Mgi Jnum | J:270542 |
| Mgi Id | MGI:6277408 | Doi | 10.1016/j.bbrc.2018.03.213 |
| Citation | Matsuzawa T, et al. (2018) Heparan sulfate in pancreatic beta-cells contributes to normal glucose homeostasis by regulating insulin secretion. Biochem Biophys Res Commun 499(3):688-695 |
| abstractText | Heparan sulfate (HS), a linear polysaccharide, is involved in diverse biological functions of various tissues. HS is expressed in pancreatic beta-cells and may be involved in beta-cell functions. However, the importance of HS for beta-cell function remains unknown. Here, we generated mice with beta-cell-specific deletion of Ext1 (betaExt1CKO), which encodes an enzyme essential for HS synthesis, to investigate the detailed roles of HS in beta-cell function. betaExt1CKO mice decreased body weights compared with control mice, despite increased food intake. Additionally, betaExt1CKO mice showed impaired glucose tolerance associated with decreased insulin secretion upon glucose challenge. Glucose-induced insulin secretion (GIIS) from isolated betaExt1CKO islets was also significantly reduced, highlighting the contribution of HS to insulin secretion and glucose homeostasis. The gene expression essential for GIIS was decreased in betaExt1CKO islets. Pdx1 and MafA were downregulated in betaExt1CKO islets, indicating that HS promoted beta-cell development and maturation. BrdU- or Ki67-positive beta-cells were reduced in betaExt1CKO pancreatic sections, suggesting the involvement of HS in the proliferation of beta-cells. Moreover, insufficient vascularization in betaExt1CKO islets may contribute to central distribution of alpha-cells. These data demonstrate HS plays diverse roles in beta-cells, and that loss of HS leads to insufficient insulin secretion and dysregulation of glucose homeostasis. |
