Exendin-4 may improve type 2 diabetes by modulating the epigenetic modifications of pancreatic histone H3 in STZ-induced diabetic C57BL/6 J mice

• Published in: Journal of physiology and biochemistry 2022-02, Vol.78 (1), p.51-59
• Main Authors: Tu, Peipei, Huang, Bin, Li, Minggang, Zhang, Yaofang, Bao, Shixiang, Tu, Na, Yang, Yanan, Lu, Jingtao
• Format: Article
• Language: English
• Subjects: Acetates; Acetylation; Animal Physiology; Animals; Beta cells; Biomedical and Life Sciences; Biomedicine; Chromatin; Diabetes; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Experimental - drug therapy; Diabetes Mellitus, Experimental - genetics; Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - genetics; Diabetes Mellitus, Type 2 - metabolism; DNA methylation; Epigenesis, Genetic; Epigenetic inheritance; Epigenetics; Exenatide; Exenatide - pharmacology; Exenatide - therapeutic use; Histone H3; Histones; Histones - genetics; Homeobox; Human Physiology; Immunoprecipitation; Methylation; Mice; Mice, Inbred C57BL; Original Article; Pancreas; Pancreatic beta cells; Polymerase chain reaction; Type 2 diabetes
• ISSN: 1138-7548; 1877-8755
• DOI: 10.1007/s13105-021-00835-8

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 μg/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.