High glucose impairs the proliferation and increases the apoptosis of endothelial progenitor cells by suppression of Akt

Nobuhisa Nakamura, Keiko Naruse, Yasuko Kobayashi, Takashi Matsuki, Yoji Hamada, Eitaro Nakashima, Hideki Kamiya, Masaki Hata, Toru Nishikawa, Atsushi Enomoto, Masahide Takahashi, Toyoaki Murohara, Tatsuaki Matsubara, Yutaka Oiso, Jiro Nakamura

Research output: Contribution to journalArticlepeer-review

21 Citations (Scopus)


Aims/Introduction: Endothelial progenitor cells (EPC) play a critical role in adult vasculogenesis and vascular repair. Previous studies have described the dysfunction of EPC in diabetic patients, but the precise mechanism is still unclear. To elucidate the dysfunction of EPC in diabetic patients, we investigated the functions and intracellular signaling of EPC under normal or high glucose conditions. We also examined the number of EPC in the peripheral blood of Japanese type 2 diabetic patients. Materials and Methods: EPC were cultured with normal or high glucose. Subsequently, the proliferation and the apoptosis of EPC were assessed in the presence or absence of vascular endothelial growth factor (VEGF). The phosphorylation of Akt was assessed by western blot analyses. We compared the number of CD34+CD45low progenitor cells, which is considered as a marker of EPC in non-diabetic and type 2 diabetic subjects, using flow cytometry. Results: High glucose decreased the proliferation of EPC and increased the number of apoptotic cells. VEGF significantly increased the proliferation and suppressed the apoptosis of EPC, both of which were abolished by PI 3-kinase inhibitor, LY294002. High glucose significantly suppressed the basal and VEGF-stimulated phosphorylation of Akt in EPC. Furthermore, the number of circulating EPC was decreased in type 2 diabetic patients, although there were no significant differences in the serum levels of VEGF between control subjects and diabetic patients. Conclusions: These findings suggest that high glucose impairs the functions of EPC through the suppression of Akt phosphorylation stimulated by VEGF.

Original languageEnglish
Pages (from-to)262-270
Number of pages9
JournalJournal of Diabetes Investigation
Issue number4
Publication statusPublished - 08-2011
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism


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