Important role of heparan sulfate in postnatal islet growth and insulin secretion

Journal Article · Fri May 22 04:00:00 EDT 2009 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/J.BBRC.2009.03.140· OSTI ID:22199700

Takahashi, Iwao; Noguchi, Naoya ^[1]; Nata, Koji ^[2]; Yamada, Shuhei; Kaneiwa, Tomoyuki; Mizumoto, Shuji ^[3]; Ikeda, Takayuki ^[1]; Sugihara, Kazushi; Asano, Masahide ^[4]; Yoshikawa, Takeo ^[1]; Yamauchi, Akiyo ^[5]; Shervani, Nausheen Jamal; Uruno, Akira ^[1]; Kato, Ichiro ^[6]; Unno, Michiaki ^[7]; Sugahara, Kazuyuki ^[3]; Takasawa, Shin ^[5]; others, and

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1. Department of Advanced Biological Sciences for Regeneration (Kotobiken Medical Laboratories), Tohoku University Graduate School of Medicine, Sendai 980-8575 (Japan)
2. Department of Medical Biochemistry, Iwate Medical University School of Pharmacy, Yahaba-cho 028-3603 (Japan)
3. Laboratory of Proteoglycan Signaling and Therapeutics, Hokkaido University Graduate School of Life Science, Sapporo 001-0021 (Japan)
4. Division of Transgenic Animal Science, Advanced Science Research Center, Kanazawa University, Kanazawa 920-8640 (Japan)
5. Department of Biochemistry, Nara Medical University, Kashihara 634-8521 (Japan)
6. Department of Biochemistry, University of Toyama Graduate School of Medicine and Pharmaceutical Sciences, Toyama 930-0194 (Japan)
7. Department of Surgery, Tohoku University Graduate School of Medicine, Sendai 980-8574 (Japan)

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.

• OSTI ID: 22199700
• Journal Information: Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 1 Vol. 383; ISSN 0006-291X; ISSN BBRCA9
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
GENES
GLUCOSE
GROWTH
INSULIN
INTERACTIONS
LIGANDS
MICE
NEOPLASMS
PANCREAS
REDUCTION
REGULATIONS
SECRETION
SULFATES