TY - JOUR
T1 - Comparison of exendin-4 on beta-cell replication in mouse and human islet grafts
AU - Tian, Lei
AU - Gao, Jie
AU - Weng, Guangbin
AU - Yi, Huimin
AU - Tian, Bole
AU - O'Brien, Timothy D.
AU - Guo, Zhiguang
PY - 2011/8
Y1 - 2011/8
N2 - Exendin-4 can stimulate β-cell replication in mice. Whether it can stimulate β-cell replication in human islet grafts remains unknown. Therefore, we compared the effects of exendin-4 on β-cell replication in mouse and human islet grafts. Islets, isolated from mouse and human donors at different ages, were transplanted into diabetic mice and/or diabetic nude mice that were given bromodeoxyuridine (BrdU) with or without exendin-4. At 4 weeks post-transplantation, islet grafts were removed for insulin and BrdU staining and quantification of insulin +/BrdU + cells. Although diabetes was reversed in all mice transplanting syngeneic mouse islets from young or old donors, normoglycemia was achieved significantly faster in exendin-4 treated mice. Mouse islet grafts in exendin-4 treated mice had significantly more insulin +/BrdU +β cells than in untreated mice (P < 0.01). Human islet grafts from ≤22-year-old donors had more insulin β cells in exendin-4 treated mice than that in untreated mice (P < 0.01). However, human islet grafts from ≥35-year-old donors contained few insulin +/BrdU +β cells in exendin-4 treated or untreated mice. Our data demonstrated that the capacity for β-cell replication in mouse and human islet grafts is different with and without exendin-4 treatment and indicated that GLP-1 agonists can stimulate β-cell replication in human islets from young donors.
AB - Exendin-4 can stimulate β-cell replication in mice. Whether it can stimulate β-cell replication in human islet grafts remains unknown. Therefore, we compared the effects of exendin-4 on β-cell replication in mouse and human islet grafts. Islets, isolated from mouse and human donors at different ages, were transplanted into diabetic mice and/or diabetic nude mice that were given bromodeoxyuridine (BrdU) with or without exendin-4. At 4 weeks post-transplantation, islet grafts were removed for insulin and BrdU staining and quantification of insulin +/BrdU + cells. Although diabetes was reversed in all mice transplanting syngeneic mouse islets from young or old donors, normoglycemia was achieved significantly faster in exendin-4 treated mice. Mouse islet grafts in exendin-4 treated mice had significantly more insulin +/BrdU +β cells than in untreated mice (P < 0.01). Human islet grafts from ≤22-year-old donors had more insulin β cells in exendin-4 treated mice than that in untreated mice (P < 0.01). However, human islet grafts from ≥35-year-old donors contained few insulin +/BrdU +β cells in exendin-4 treated or untreated mice. Our data demonstrated that the capacity for β-cell replication in mouse and human islet grafts is different with and without exendin-4 treatment and indicated that GLP-1 agonists can stimulate β-cell replication in human islets from young donors.
KW - GLP-1
KW - beta-cell regeneration
KW - beta-cell replication
KW - exendin-4
KW - islet transplantation
UR - http://www.scopus.com/inward/record.url?scp=79960136744&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79960136744&partnerID=8YFLogxK
U2 - 10.1111/j.1432-2277.2011.01275.x
DO - 10.1111/j.1432-2277.2011.01275.x
M3 - Article
C2 - 21627696
AN - SCOPUS:79960136744
SN - 0934-0874
VL - 24
SP - 856
EP - 864
JO - Transplant International
JF - Transplant International
IS - 8
ER -