Divergent Effect of Central Incretin Receptors Inhibition in a Rat Model of Sporadic Alzheimer’s Disease

Scientific paper - Original scientific paper

• Author: Jelena Osmanović Barilar
• Author: Ana Knezović
• Author: Jan Homolak
• Author: Ana Babić Perhoč
• Author: Melita Šalković-Petrišić
• Author's institution: University of Zagreb; School of Medicine; (Department of Pharmacology)
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Basic Medical Sciences; Pharmacology

Abstract (english)

The incretin system is an emerging new field that might provide valuable contributions to the research of both the pathophysiology and therapeutic strategies in the treatment of diabetes, obesity, and neurodegenerative disorders. This study aimed to explore the roles of central glucagon-like peptide-1 (GLP-1) and gastric inhibitory polypeptide (GIP) on cell metabolism and energy in the brain, as well as on the levels of these incretins, insulin, and glucose via inhibition of the central incretin receptors following intracerebroventricular administration of the respective antagonists in healthy rats and a streptozotocin-induced rat model of sporadic Alzheimer’s disease (sAD). Chemical ablation of the central GIP receptor (GIPR) or GLP-1 receptor (GLP-1R) in healthy and diseased animals indicated a region-dependent role of incretins in brain cell energy and metabolism and central incretin-dependent modulation of peripheral hormone secretion, markedly after GIPR inhibition, as well as a dysregulation of the GLP-1 system in experimental sAD.

• Keywords (english): AMP-Activated Protein Kinases / metabolism; Alzheimer Disease / etiology; Alzheimer Disease / metabolism; Alzheimer Disease / pathology; Animals; Biomarkers; Brain / metabolism; Brain / pathology; Disease Models, Animal; Disease Susceptibility; Gastric Inhibitory Polypeptide / metabolism; Glucagon-Like Peptide Receptors / antagonists & inhibitors; Glucagon-Like Peptide Receptors / genetics; Glucagon-Like Peptide Receptors / metabolism; Glucose / metabolism; Insulin / metabolism; Neurons / pathology; Rats
• Language: english
• Publication type: Scientific paper - Original scientific paper
• Publication status: Published
• Peer review: Peer review
• Publication version: Published version
• Journal title: International Journal of Molecular Sciences
• Numbering: vol. 23, no. 1, 548
• e-ISSN: 1422-0067
• DOI: https://doi.org/10.3390/ijms23010548
• URN:NBN: urn:nbn:hr:105:792760
• Publication: 2022-01-04
• Document URL: https://www.mdpi.com/1422-0067/23/1/548
• Type of resource: Text
• Access conditions: Open access
• Created on: 2022-07-06 10:59:06