Morphological and functional adaptation of pancreatic islet blood vessels to insulin resistance is impaired in diabetic db/db mice

Yuka Okajima, Takashi Matsuzaka*, Shun Miyazaki, Kaori Motomura, Hiroshi Ohno, Rahul Sharma, Takuya Shimura, Nurani Istiqamah, Song iee Han, Yuhei Mizunoe, Yoshinori Osaki, Hitoshi Iwasaki, Shigeru Yatoh, Hiroaki Suzuki, Hirohito Sone, Takafumi Miyamoto, Yuichi Aita, Yoshinori Takeuchi, Motohiro Sekiya, Naoya YahagiYoshimi Nakagawa, Tsutomu Tomita, Hitoshi Shimano*

*この論文の責任著者

研究成果: ジャーナルへの寄稿学術論文査読

11 被引用数 (Scopus)

抄録

The pancreatic islet vasculature is of fundamental importance to the β-cell response to obesity-associated insulin resistance. To explore islet vascular alterations in the pathogenesis of type 2 diabetes, we evaluated two insulin resistance models: ob/ob mice, which sustain large β-cell mass and hyperinsulinemia, and db/db mice, which progress to diabetes due to secondary β-cell compensation failure for insulin secretion. Time-dependent changes in islet vasculature and blood flow were investigated using tomato lectin staining and in vivo live imaging. Marked islet capillary dilation was observed in ob/ob mice, but this adaptive change was blunted in db/db mice. Islet blood flow volume was augmented in ob/ob mice, whereas it was reduced in db/db mice. The protein concentrations of total and phosphorylated endothelial nitric oxide synthase (eNOS) at Ser1177 were increased in ob/ob islets, while they were diminished in db/db mice, indicating decreased eNOS activity. This was accompanied by an increased retention of advanced glycation end-products in db/db blood vessels. Amelioration of diabetes by Elovl6 deficiency involved a restoration of capillary dilation, blood flow, and eNOS phosphorylation in db/db islets. Our findings suggest that the disability of islet capillary dilation due to endothelial dysfunction impairs local islet blood flow, which may play a role in the loss of β-cell function and further exacerbate type 2 diabetes.

本文言語英語
論文番号166339
ジャーナルBiochimica et Biophysica Acta - Molecular Basis of Disease
1868
4
DOI
出版ステータス出版済み - 2022/04/01

ASJC Scopus 主題領域

  • 分子医療
  • 分子生物学

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