Liraglutide Activates AMPK Signaling and Partially Restores Normal Circadian Rhythm and Insulin Secretion in Pancreatic Islets in Diabetic Mice

Kexin Wang; Yu Sun; Peng Lin; Jun Song; Ruxing Zhao; Wenjuan Li; Xinguo Hou; Chuan Wang; Lingshu Wang; Ping Zhu; Li Chen

doi:10.1248/bpb.b15-00024

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Liraglutide Activates AMPK Signaling and Partially Restores Normal Circadian Rhythm and Insulin Secretion in Pancreatic Islets in Diabetic Mice

Kexin Wang, Yu Sun, Peng Lin, Jun Song, Ruxing Zhao, Wenjuan Li, Xinguo Hou, Chuan Wang, Lingshu Wang, Ping Zhu, Li Chen

Author information

Kexin Wang
Department of General Surgery, Qilu Hospital of Shandong University
Yu Sun
Department of Endocrinology, Qilu Hospital of Shandong University
Peng Lin
Department of Endocrinology, Qilu Hospital of Shandong University
Jun Song
Department of Endocrinology, Qilu Hospital of Shandong University
Ruxing Zhao
Department of Endocrinology, Qilu Hospital of Shandong University
Wenjuan Li
Department of Endocrinology, Qilu Hospital of Shandong University
Xinguo Hou
Department of Endocrinology, Qilu Hospital of Shandong University
Chuan Wang
Department of Endocrinology, Qilu Hospital of Shandong University
Lingshu Wang
Department of Endocrinology, Qilu Hospital of Shandong University
Ping Zhu
Department of Ophthalmology, College of Medicine, University of Florida
Li Chen Corresponding author
Department of Endocrinology, Qilu Hospital of Shandong University
Institute of Endocrinology and Metabolism, Shandong University

Keywords: β-cell function, glucagon-like peptide-1 (GLP-1), circadian clock, 5′ AMP-activated protein kinase (AMPK)

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Supplementary material

2015 Volume 38 Issue 8 Pages 1142-1149

DOI https://doi.org/10.1248/bpb.b15-00024

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Abstract

β-Cell insufficiency plays an important role in the development of diabetes. Environmental factors, including lifestyle, play a critical role in β-cell dysfunction. Modern lifestyles affect the inherent circadian clock in central and peripheral organs. Recent studies have demonstrated that the normal intrinsic circadian clock in islets was essential for the viability of β cells and their insulin secretory function. Overall, however, the data are inconclusive. Our study demonstrated that the disrupted circadian rhythm of islets in streptozotocin induced type1 diabetic mice may be associated with impaired β-cell function and glucose intolerance. Liraglutide, a glucagon-like peptide-1 (GLP-1) analogue, could partially restore the normal circadian rhythm and activate the 5′ AMP-activated protein kinase (AMPK) signaling pathway. Our study provided evidence demonstrating that Liraglutide might restore β-cell function and protect against the development of diabetes in a mouse model by attenuating the disruption of the intrinsic circadian rhythm in islets and by activating AMPK signaling.

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