Journal
JOURNAL OF PHYSIOLOGY AND BIOCHEMISTRY
Volume 78, Issue 1, Pages 51-59Publisher
SPRINGER
DOI: 10.1007/s13105-021-00835-8
Keywords
Type 2 diabetes; Epigenetics; Exendin-4; Histone H3; Pdx 1
Categories
Funding
- Key Technologies R&D Program of Tianjin [14ZCZDSY00013]
- National Natural Science Foundation of China [81773105]
- Scientific Research Fund Projects of Anhui Medical University [2018xky011]
- University Natural Science Research Project of Anhui Province [KJ2020A0159]
Ask authors/readers for more resources
Type 2 diabetes (T2D) is a complex systemic disease that might benefit from treatment with exendin-4, as shown in this study on C57BL/6 J mice. The study investigated epigenetic alterations in pancreatic tissues of diabetic mice and demonstrated an improvement in T2D progression with exendin-4 treatment through modulation of histone acetylation and methylation patterns. Understanding these epigenetic changes may lead to novel therapeutic approaches for T2D.
Type 2 diabetes (T2D) is a complicated systemic disease that might be improved by exendin-4, although the epigenetic role remains unclear. In the current study, C57BL/6 J mice were used to generate a T2D model, followed by treatment with exendin-4 (10 mu g/kg). Histone H3K9 and H3K23 acetylation, H3K4 mono-methylation, and H3K9 di-methylation were explored by western blot analysis of pancreatic histone extracts. Real-time polymerase chain reaction (PCR) was used to examine the expression levels of pancreatic beta cell development-related genes, and chromatin immunoprecipitation (ChIP) was applied to analyze H3 and H3K9 acetylation, H3K4 mono-methylation, and H3K9 di-methylation in the promoter region of the pancreatic and duodenal homeobox 1 (Pdx1) gene. The results showed that total H3K9 di-methylation and H3K9 and H3K23 acetylation increased in pancreatic tissues of diabetic mice, whereas H3K4 mono-methylation was reduced. All of these changes could be abrogated by treatment with exendin-4. Our data indicated that T2D progression might be improved by exendin-4 treatment through the reversal of global pancreatic histone H3K9 and H3K23 acetylation, H3K4 mono-methylation, and H3K9 di-methylation. A better understanding of these epigenetic alterations may, therefore, lead to novel therapeutic strategies for T2D.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available