, Volume 54, Issue 2, pp 383–395 | Cite as

Inhibition of tumor suppressor p53 preserves glycation-serum induced pancreatic beta-cell demise

  • Y. Li
  • T. Zhang
  • Q. Huang
  • Y. Sun
  • X. Chang
  • H. Zhang
  • Y. ZhuEmail author
  • X. HanEmail author
Original Article


Tumor suppressor p53 is a transcriptional factor that determines cell fate in response to multiple stressors, such as oxidative stress and endoplasmic reticulum stress, in the majority of cells. However, its role in pancreatic beta cells is not well documented. Our previous research has revealed that glycation-serum (GS) induced pancreatic beta-cell demise through the AGEs-RAGE pathway. In the present study, we investigated the role of p53 in GS-related beta-cell demise. Using pancreatic islets beta-cell line INS-1 cells, we found that with GS treatment, the transcriptional activity of p53 was significantly evoked due to the increased amount of nuclear p53 protein. Resveratrol (RSV) was capable of further enhancing this transcriptional ability and consequently increased the population of dead beta cells under GS exposure. In contrast, inhibiting this transcriptional activity via p53 interference greatly protected beta cells from the damage provoked by GS, as well as damage strengthened by RSV. However, the pharmacological activation of PPARγ with troglitazone (TRO) only suppressed GS-induced, not RSV-induced, p53 activity. Moreover, the activation of PPARγ greatly preserved beta cells from GS-induced death. This protective effect recurred due to improved mitochondrial function with Bcl2 overexpression. Further, p53 activation could induce cellular apoptosis in primary rat islets. Our findings explore the broader role of p53 in regulating pancreatic beta-cell demise in the presence of GS and may provide a therapeutic target for the treatment and prevention of diabetes.


p53 Glycation-serum Pancreatic beta-cell demise Diabetes 



This study was supported by research grants from (1) the National Natural Science Foundation of China (81420108007) and the National Basic Research Program of China (973 Program, 2012CB524903) to XH, (2) the National Natural Science Foundation of China (81200559) to YZ, and (3) the National Natural Science Foundation of China (81472989) to HZ. XH is a Fellow at the Collaborative Innovation Center for Cardiovascular Disease Translational Medicine.

Compliance with ethical standards

Conflict of interest

The authors took part in the conception and design of the study, as well as either drafting or critically revising the manuscript. The authors have approved the final version of the manuscript.

Supplementary material

12020_2016_979_MOESM1_ESM.doc (38 kb)
Supplementary material 1 (DOC 39 kb)
12020_2016_979_MOESM2_ESM.tif (345 kb)
Supplemental Figure 1 Analysis of transcriptional activities with GS treatment. INS-1 cells were co-transfected with Myc-luc, ARE-luc, Rb-luc, AP-1-luc, NF-κB-luc and pRL-CMV (10:1) constructs for 24 h, followed by treatment with NG or 10 % GS for a further 24 h. Lysates were harvested for the dual-luciferase reporter assay. The firefly luciferase activity representing report genes activity was normalized to the Renilla activity. The data represent three separate experiments. **p<0.01 versus NG (TIFF 346 kb)
12020_2016_979_MOESM3_ESM.tif (2.8 mb)
Supplemental Figure 2 p53 binding specificity examination. INS-1 cells were in the presence of NG or 10 % GS for 2 h, and then, nuclear proteins were extracted for EMSA assay. (a) Unlabeled p53 probe was used to identify the binding specificity. (b) An anti-p53 antibody was used to identify the binding specificity (TIFF 2822 kb)
12020_2016_979_MOESM4_ESM.tif (3.4 mb)
Supplementary material 4 (TIFF 3468 kb)
12020_2016_979_MOESM5_ESM.tif (2.1 mb)
Supplementary material 5 (TIFF 2133 kb)


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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  1. 1.Key Laboratory of Human Functional Genomics of Jiangsu Province, Jiangsu Diabetes CenterNanjing Medical UniversityNanjingChina
  2. 2.Department of Obstetrics and GynecologyFirst Affiliated Hospital of Nanjing Medical UniversityNanjingChina

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