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J Diabetes Complications. 2018 Nov;32(11):985-994. doi: 10.1016/j.jdiacomp.2018.08.002. Epub 2018 Aug 5.

Liraglutide protects β-cell function by reversing histone modification of Pdx-1 proximal promoter in catch-up growth male rats.

Author information

1
Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei, China; Department of Endocrinology, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei, China.
2
Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei, China.
3
Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei, China; Department of Endocrinology, Wuhan No.1 Hospital, Wuhan 430022, Hubei, China.
4
Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei, China. Electronic address: lhqing5@126.com.

Abstract

AIMS:

Catch-up growth after a period of nutritional deprivation in adulthood is related to the onset of metabolic disorders. This process involves chromatin remodelling of the Pdx-1 gene in pancreas. The objective of this study was to determine the chromatin remodelling mechanism of GLP-1 analogue Liraglutide upon Pdx-1 in catch-up growth rats in vivo and in vitro.

METHODS:

Five-week-old male specific pathogen free (SPF) Wistar rats were randomly divided into normal group, catch-up growth group and Liraglutide group. Hyperglycemic clamp test and glucose-stimulated insulin secretion test were carried out to evaluate β-cell function in vivo and in vitro. The histone H3 modification changes at the Pdx-1 proximal promoter were assessed by chromatin immunoprecipitation.

RESULTS:

The catch-up growth state was characterized by less recruitment of histone H3 lysine4 trimethylation and histone H3 acetylation and more recruitment of histone H3 lysine9 dimethylation at the Pdx-1 proximal promoter. Liraglutide treatment reversed these epigenetic changes and increased Pdx-1 expression, which could be abrogated by GLP-1 receptor antagonist Exendin 9-39. The β-cell function of catch-up growth rats was improved after Liraglutide treatment.

CONCLUSIONS:

The protective effects of Liraglutide on pancreatic islet β-cell function may be related to histone H3 modification at the Pdx-1 proximal promoter during catch-up growth and could be used to treat catch-up growth-related metabolic disorders.

KEYWORDS:

Catch-up growth; Histone modification; Liraglutide; Pdx-1; β-Cell function

PMID:
30177467
DOI:
10.1016/j.jdiacomp.2018.08.002
[Indexed for MEDLINE]

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