IGF-Ⅱrestores rapamycin-induced suppression of β-cell differentiation and expansion of adult pancreas stem cells
10.3760/cma.j.issn.1000-6699.2018.08.010
- VernacularTitle:胰岛素样生长因子Ⅱ及雷帕霉素的联合干预在胰腺干细胞分化中的保护机制研究
- Author:
Haimin WANG
1
;
Gang WANG
;
Ruoxuan PENG
;
Qin XU
;
Yufeng DENG
;
Hong ZHANG
;
Yakun FENG
;
Xianchao XIAO
;
Ying GAO
;
Chenglin SUN
Author Information
1. 吉林大学第一医院内分泌代谢科
- Keywords:
Porcine neonatal pancreas cell clusters;
Rapamycin;
Insulin-like growth factor-Ⅱ;
β-cell;
Adultpancreas stem cells
- From:Chinese Journal of Endocrinology and Metabolism
2018;34(8):678-683
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the mechanism of rapamycin inhibiting the differentiation and proliferation of newborn porcine pancreatic adult stem cells, and to explore the therapeutic methods that may effectively reduce the side effects of rapamycin. Method Porcine NPCCs were treated with rapamycin alone or in combination with IGF-Ⅱ, and the caspase-3 and [ 3 H ]-thymidine uptake assays were performed to detect apoptosis and proliferation. The expression of insulin, PDX-1, NeuroD/Beta2, and Foxo1, a downstream transcription factor of IGF-Ⅱ, were analyzed by RT-PCR and Western blot to evaluate the differentiation ability of pancreatic adult stem cells. Results The NPCCs treated with rapamycin inhibited the proliferation ofβ-cells, increased apoptosis, reduced insulin secretion, inhibited the expression of PDX-1 and NeuroD/Beta2, and decreased the expression of IGF-Ⅱ. Foxo1 expression and induction of Foxo1 from the cytoplasm to the nucleus of the ectopic. The combined treatment of rapamycin and IGF-Ⅱcan reduce the side effects of rapamycin, inhibit the decrease ofβ-cell number and insulin content, repair the expression of insulin, PDX-1, NeuroD/Beta2, inhibit Foxo1 expression and intracellular ectopic. Conclusion Aberrant expression of IGF-Ⅱ and Foxol genes is the key inducing factor of rapamycin inhibiting the proliferation and differentiation of NPCCs, and IGF-Ⅱtreatment can effectively reduce the side effects of rapamycin on NPCCs differentiation.
