The therapeutic potential of glucagon-like peptide-1 receptor analogs for neuroinflammation in the setting of asthma

Abstract

Glucagon-like peptide-1 (GLP-1) is a hormone that regulates blood glucose levels and is produced by the enteroendocrine glands in the large and small intestines in response to the consumption of foods that contain carbohydrates, fats, and proteins. When GLP-1 is secreted, it acts on the pancreas to increase insulin production and secretion, while decreasing pancreatic glucagon secretion in order to lower serum glucose. However, GLP-1 also regulates metabolism through the gut-brain axis. While GLP-1 is primarily produced in the gut and released into the bloodstream, small quantities of it can also be synthesized in distinct areas of neurons located in the hindbrain. Recent studies have proposed that GLP-1 receptor (GLP-1R) agonists (GLP-1RAs) may protect against neuroinflammatory diseases. GLP-1RAs may also be a therapeutic target for asthma as animal models show that these drugs reduce allergen-induced airway inflammation, as the GLP-1R is expressed on lung epithelial and endothelial cells. There is a notable association between insulin resistance and the onset of asthma, particularly among obese people, with this association suggesting that metabolic dysfunction may play a role in asthma development. There is also evidence that there may be a link between asthma pathobiology and neuroinflammation, suggesting that GLP-1 and its analogs may regulate neuroinflammatory pathways that contribute to asthma pathogenesis. Interest is growing, though research remains limited, in how inflammation in the nervous system and lung might be linked. This review will explore how GLP-1R signaling could inhibit interdependent inflammation in both the lung and nervous system. This review will first focus on the inflammation that is known to exist in asthma, then pivot to the current state of neural regulation of asthma, and finally speculate on how GLP-1RA signaling could inhibit both neural and lung inflammation in asthma treatment.

Keywords

Glucagon-like peptide-1 receptor / glucagon-like peptide-1 receptor agonist / asthma / neuroinflammation

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