[Effects of GLP-1 treatment on protection of B cells in Otsuka Long-Evans Tokushima fatty rats].
OBJECTIVE
To investigate the effect of GLP-1 on the blood glucose in type 2 diabetic rats, and its protective effects on the islet B cells.


METHODS
Thirty rats were divided into three groups: spontaneous type 2 diabetes animal model OLETF rats, GLP-1 [from the twelfth week 56 micro/(kg.d), sc] therapy group and LETO rats as control. In the 14th and 20th weeks, standard OGTT including fast and 2 h-plasma glucose were measured respectively. In the 14th weeks, 3 rats from each group were killed randomly, and the rest of the rats were killed until the 20th week. Immunostaining with the marker of PCNA, TUNEL, and insulin assessed metabolic changes in the islet. Ultrastructure of the B cell was observed with the electronic microscope.


RESULTS
In the 14th and 20th week, AUC for insulin were higher in treated animals (10.86+/-1.56 vs. 9.07+/-1.28, P<0.01) and (13.00+/-1.50 vs. 10.35+/-0.86, P<0.01), which was paralleled by a decrease in AUC for glucose, (29.93+/-3.15 vs. 34.99+/-4.30, P<0.01) and (38.37+/-3.18 vs. 42.38+/-2.37, P<0.01). Ex vivo immunostaining with the marker of cell proliferation, PCNA, showed that the metabolic changes observed in rats treated with GLP-1 were associated with an increase in cell proliferation of the B cell (48.9+/-39.6 vs. 39.6+/-9.3, P<0.05). TUNEL staining, a marker of cellular apoptosis, indicated a reduction of apoptotic cells within the islet in GLP-1-treated rats (24.8+/-4.2 vs. 30.8+/-5.8, P<0.01). Immunostaining for the insulin showed a significant increase in insulin content in GLP-1-treated animals. GLP-1-treatment ameliorated the ultrastructure of the B cell.


CONCLUSIONS
Our findings have provided evidence that the beneficial effects of GLP-1 in OLETF rats are mediated by an increase in islet cell proliferation and a decrease of cellular apoptosis.
Wang
Yu
Y
Department of Endocrinology, Peking University First Hospital, Beijing 100034, China.
Guo
Xiao-hui
XH
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000473:pathology; D052216:Glucagon-Like Peptide 1 / Q000627:therapeutic use*; D007150:Immunohistochemistry; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D020011:Protective Agents / Q000627:therapeutic use; D011897:Random Allocation; D051381:Rats; D020334:Rats, Inbred OLETF
D018809:Proliferating Cell Nuclear Antigen; D020011:Protective Agents; D052216:Glucagon-Like Peptide 1