Glucagon-like Peptide-1 and the Central/Peripheral Nervous System: Crosstalk in Diabetes

Trends Endocrinol Metab. 2017 Feb;28(2):88-103. doi: 10.1016/j.tem.2016.10.001. Epub 2016 Oct 27.

Abstract

Glucagon-like peptide-1 (GLP-1) is released in response to meals and exerts important roles in the maintenance of normal glucose homeostasis. GLP-1 is also important in the regulation of neurologic and cognitive functions. These actions are mediated via neurons in the nucleus of the solitary tract that project to multiple regions expressing GLP-1 receptors (GLP-1Rs). Treatment with GLP-1R agonists (GLP-1-RAs) reduces ischemia-induced hyperactivity, oxidative stress, neuronal damage and apoptosis, cerebral infarct volume, and neurologic damage, after cerebral ischemia, in experimental models. Ongoing human trials report a neuroprotective effect of GLP-1-RAs in Alzheimer's and Parkinson's disease. In this review, we discuss the role of GLP-1 and GLP-1-RAs in the nervous system with focus on GLP-1 actions on appetite regulation, glucose homeostasis, and neuroprotection.

Trial registration: ClinicalTrials.gov NCT01255163 NCT01469351 NCT01843075.

Keywords: appetite; central nervous system; glucagon-like peptide-1; neurodegenerative diseases; type 2 diabetes.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Central Nervous System / metabolism*
  • Diabetes Mellitus / metabolism*
  • Diabetes Mellitus, Type 2 / metabolism
  • Glucagon-Like Peptide 1 / metabolism*
  • Humans
  • Neurodegenerative Diseases / metabolism
  • Peripheral Nervous System / metabolism*

Substances

  • Glucagon-Like Peptide 1

Associated data

  • ClinicalTrials.gov/NCT01255163
  • ClinicalTrials.gov/NCT01469351
  • ClinicalTrials.gov/NCT01843075