Synergistic Effect of Hyperglycemia and p27kip1 Suppression on Adult Mouse Islet Beta Cell Replication

被引:4
作者
Chen, Szu-Tah [1 ,2 ]
Fu, Shin-Huei [3 ,4 ]
Hsu, Samuel [1 ,2 ]
Huang, Yu-Yao [1 ,2 ]
Hsu, Brend Ray-Sea [1 ,2 ]
机构
[1] Chang Gung Med Ctr, Dept Internal Med, Div Endocrinol & Metab, Tao Yuan 333, Taiwan
[2] Chang Gung Univ, Tao Yuan 333, Taiwan
[3] Natl Def Med Ctr, Grad Inst Life Sci, Taiwan Int Grad Program, Taipei 115, Taiwan
[4] Acad Sinica, Taipei 115, Taiwan
关键词
DEPENDENT KINASE INHIBITORS; CYCLE PROGRESSION; GLUCOSE; GROWTH; UBIQUITIN; PROLIFERATION; PROTEINS; COMPLEX;
D O I
10.1155/2012/417390
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The complementary role of hyperglycemia and p27(kip1) suppression on islet beta cell regeneration was investigated in a syngeneic mouse model. p27(kip1) gene silencing was performed by infecting islets of C57BL/6 with shRNA lentiviral particles. At 54 hours after viral infection, p27(kip1) protein content in cultured targeting islets was 22% of that in freshly isolated islets. Six days after transplantation to diabetic mice, targeting islet graft had considerably more cells with Ki67-staining nuclei than nontargeting islets. The mice in the targeting-islet group had a significantly shorter duration of temporary hyperglycaemia than mice in the non-targeting-islet group. The long-term ex vivo beneficial effect of p27(kip1) silencing on graft function was also indicated by the significantly higher cumulative cure rate for diabetes in mice receiving 200 targeting islets than that in mice receiving 200 nontargeting islets. Our data suggest that hyperglycemia and persistent p27(kip1) suppression have a synergistic effect on islet beta cell replication in adult mice.
引用
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页数:7
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