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


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(+)CD45(low) 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. (J Diabetes Invest, doi: 10.1111/j.2040-1124.2010.00093.x, 2011).
Departments of Pathology.
Nobuhisa
N
Nakamura
Department of Internal Medicine, School of Dentistry, Aichi-Gakuin University ; Endocrinology and Diabetes.
Keiko
K
Naruse
Department of Internal Medicine, School of Dentistry, Aichi-Gakuin University.
Yasuko
Y
Kobayashi
Endocrinology and Diabetes.
Takashi
T
Matsuki
Departments of Metabolic Diseases.
Yoji
Y
Hamada
Diabetes Center, Chubu Rosai Hospital, Nagoya, Japan.
Eitaro
E
Nakashima
CKD Initiatives, Nagoya University School of Medicine.
Hideki
H
Kamiya
Department of Internal Medicine, School of Dentistry, Aichi-Gakuin University.
Masaki
M
Hata
Department of Internal Medicine, School of Dentistry, Aichi-Gakuin University.
Toru
T
Nishikawa
Departments of Pathology.
Atsushi
A
Enomoto
Departments of Pathology.
Masahide
M
Takahashi
Cardiology, Nagoya University Graduate School of Medicine.
Toyoaki
T
Murohara
Department of Internal Medicine, School of Dentistry, Aichi-Gakuin University.
Tatsuaki
T
Matsubara
Endocrinology and Diabetes.
Yutaka
Y
Oiso
Endocrinology and Diabetes.
Jiro
J
Nakamura
Akt; Endothelial progenitor cells; Vascular endothelial growth factor