Reduceds β-cell proliferation and impaired glucose tolerance in pancreatics β-cell specific Extl3 knockout mice.

EXTL3作为糖基转移酶参与硫酸肝素蛋白聚糖的生物合成。我们产生胰腺β细胞特异性Extl3敲除（βExtl3 3ko）小鼠。2-8周龄的β ext3ko小鼠，β细胞增殖活性降低，胰岛组织学检查显示为非典型组织。8周龄的β ext3ko小鼠在葡萄糖刺激下表现出葡萄糖耐受不良，并伴有胰岛素分泌受损。这些数据表明硫酸肝素在β细胞增殖和胰岛素分泌机制中起重要作用。

EXTL3 functions as a glycosyltransferase involved in heparan sulfate proteoglycans biosynthesis. We generated pancreatic β-cell specific Extl3 knockout (βExtl3KO) mice. In βExtl3KO mice at 2-8 weeks old, the β-cell proliferation activity was decreased and histological examination of pancreatic islets revealed an atypical organization. βExtl3KO mice at 8 weeks old showed glucose intolerance coupled to impaired insulin secretion upon glucose challenge. These data indicate that heparan sulfate plays important role(s) in β-cell proliferation and the mechanism of insulin secretion.