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

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.

• Authors: Kexin Wang, Yu Sun, Peng Lin, Jun Song, Ruxing Zhao, Wenjuan Li, Xinguo Hou, Chuan Wang, Lingshu Wang, Ping Zhu, Li Chen
• Journal: Biological & pharmaceutical bulletin (Biol Pharm Bull) Vol. 38 Issue 8 Pg. 1142-9 ( 2015) ISSN: 1347-5215 [Electronic] Japan
• PMID: 26040899 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Hypoglycemic Agents
• Insulin
• Liraglutide
• Glucagon-Like Peptide 1
• AMP-Activated Protein Kinases
• Glucose

Topics

• AMP-Activated Protein Kinases (metabolism)
• Animals
• Circadian Rhythm (drug effects)
• Diabetes Mellitus, Experimental (drug therapy, metabolism)
• Glucagon-Like Peptide 1 (analogs & derivatives, metabolism)
• Glucose (metabolism)
• Glucose Intolerance (drug therapy, metabolism, physiopathology)
• Hypoglycemic Agents (pharmacology, therapeutic use)
• Insulin (metabolism)
• Insulin Secretion
• Insulin-Secreting Cells (drug effects, metabolism)
• Islets of Langerhans (drug effects, metabolism, physiology)
• Liraglutide (pharmacology, therapeutic use)
• Male
• Mice, Inbred C57BL
• Phosphorylation
• Signal Transduction