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.
机构:Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA
Franklin, DS
Godfrey, VI
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机构:Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA
Godfrey, VI
O'Brien, DA
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机构:Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA
O'Brien, DA
Deng, CX
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机构:Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA
Deng, CX
Xiong, Y
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Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USAUniv N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA
机构:
Chonnam Natl Univ, Coll Vet Med, Dept Vet Physiol, Kwangju 500757, South KoreaChonnam Natl Univ, Coll Vet Med, Dept Vet Physiol, Kwangju 500757, South Korea
机构:Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA
Franklin, DS
Godfrey, VI
论文数: 0引用数: 0
h-index: 0
机构:Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA
Godfrey, VI
O'Brien, DA
论文数: 0引用数: 0
h-index: 0
机构:Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA
O'Brien, DA
Deng, CX
论文数: 0引用数: 0
h-index: 0
机构:Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA
Deng, CX
Xiong, Y
论文数: 0引用数: 0
h-index: 0
机构:
Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USAUniv N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA
机构:
Chonnam Natl Univ, Coll Vet Med, Dept Vet Physiol, Kwangju 500757, South KoreaChonnam Natl Univ, Coll Vet Med, Dept Vet Physiol, Kwangju 500757, South Korea