Important role of heparan sulfate in postnatal islet growth and insulin secretion.
Heparan sulfate (HS) binds with several signaling molecules and regulates ligand-receptor interactions, playing an essential role in embryonic development. Here we showed that HS was intensively expressed in pancreatic islet beta-cells after 1 week of age in mice. The enzymatic removal of HS in isolated islets resulted in attenuated glucose-induced insulin secretion with a concomitant reduction in gene expression of several key components in the insulin secretion machinery. We further depleted islet HS by inactivating the exostosin tumor-like 3 gene specifically in beta-cells. These mice exhibited abnormal islet morphology with reduced beta-cell proliferation after 1 week of age and glucose intolerance due to defective insulin secretion. These results demonstrate that islet HS is involved in the regulation of postnatal islet maturation and required to ensure normal insulin secretion.
Takahashi
Iwao
I
Department of Advanced Biological Sciences for Regeneration, Tohoku University Graduate School of Medicine, Sendai, Japan.
Noguchi
Naoya
N
Nata
Koji
K
Yamada
Shuhei
S
Kaneiwa
Tomoyuki
T
Mizumoto
Shuji
S
Ikeda
Takayuki
T
Sugihara
Kazushi
K
Asano
Masahide
M
Yoshikawa
Takeo
T
Yamauchi
Akiyo
A
Shervani
Nausheen Jamal
NJ
Uruno
Akira
A
Kato
Ichiro
I
Unno
Michiaki
M
Sugahara
Kazuyuki
K
Takasawa
Shin
S
Okamoto
Hiroshi
H
Sugawara
Akira
A