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

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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.