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J Diabetes Investig. 2016 Apr;7 Suppl 1:64-9. doi: 10.1111/jdi.12464. Epub 2016 Mar 31.

Neural effects of gut- and brain-derived glucagon-like peptide-1 and its receptor agonist.

Author information

1
Division of Integrative PhysiologyDepartment of PhysiologyJichi Medical University School of MedicineShimotsukeTochigiJapan; Division of Cardiovascular MedicineDepartment of Internal MedicineJichi Medical University School of MedicineShimotsukeTochigiJapan.
2
Division of Integrative Physiology Department of Physiology Jichi Medical University School of Medicine Shimotsuke Tochigi Japan.

Abstract

Glucagon-like peptide-1 (GLP-1) is derived from both the enteroendocrine L cells and preproglucagon-expressing neurons in the nucleus tractus solitarius (NTS) of the brain stem. As GLP-1 is cleaved by dipeptidyl peptidase-4 yielding a half-life of less than 2 min, it is plausible that the gut-derived GLP-1, released postprandially, exerts its effects on the brain mainly by interacting with vagal afferent neurons located at the intestinal or hepatic portal area. GLP-1 neurons in the NTS widely project in the central nervous system and act as a neurotransmitter. One of the physiological roles of brain-derived GLP-1 is restriction of feeding. GLP-1 receptor agonists have recently been used to treat type 2 diabetic patients, and have been shown to exhibit pleiotropic effects beyond incretin action, which involve brain functions. GLP-1 receptor agonist administered in the periphery is stable because of its resistance to dipeptidyl peptidase-4, and is highly likely to act on the brain by passing through the blood-brain barrier (BBB), as well as interacting with vagal afferent nerves. Central actions of GLP-1 have various roles including regulation of feeding, weight, glucose and lipid metabolism, cardiovascular functions, cognitive functions, and stress and emotional responses. In the present review, we focus on the source of GLP-1 and the pathway by which peripheral GLP-1 informs the brain, and then discuss recent findings on the central effects of GLP-1 and GLP-1 receptor agonists.

KEYWORDS:

Brain stem; Cardiovascular; Feeding

PMID:
27186358
PMCID:
PMC4854507
DOI:
10.1111/jdi.12464
[Indexed for MEDLINE]
Free PMC Article

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