GLP-1a: Going beyond Traditional Use

Abstract

Glucagon-like peptide-1 (GLP-1) is a human incretin hormone derived from the proglucagon molecule. GLP-1 receptor agonists are frequently used to treat type 2 diabetes mellitus and obesity. However, the hormone affects the liver, pancreas, brain, fat cells, heart, and gastrointestinal tract. The objective of this study was to perform a systematic review on the use of GLP-1 other than in treating diabetes. PubMed, Cochrane, and Embase were searched, and the PRISMA guidelines were followed. Nineteen clinical studies were selected. The results showed that GLP-1 agonists can benefit defined off-medication motor scores in Parkinson’s Disease and improve emotional well-being. In Alzheimer’s disease, GLP-1 analogs can improve the brain’s glucose metabolism by improving glucose transport across the blood–brain barrier. In depression, the analogs can improve quality of life and depression scales. GLP-1 analogs can also have a role in treating chemical dependency, inhibiting dopaminergic release in the brain’s reward centers, decreasing withdrawal effects and relapses. These medications can also improve lipotoxicity by reducing visceral adiposity and decreasing liver fat deposition, reducing insulin resistance and the development of non-alcoholic fatty liver diseases. The adverse effects are primarily gastrointestinal. Therefore, GLP-1 analogs can benefit other conditions besides traditional diabetes and obesity uses.

Protection against stroke with glucagon-like peptide-1 receptor agonists: a comprehensive review of potential mechanisms

“…Within the cardiovascular system, GLP-1 receptors are expressed on endothelial cells, monocytes, macrophages, and vascular smooth muscle cells (VSMCs) [ 9 ]. GLP-1 receptors are also widely expressed in the central nervous system, including the brainstem, cerebellum, hippocampus, cortex, hypothalamus, and amygdala [ 7 , 10 , 11 ]. There, the cellular expression of GLP-1 receptors is predominantly confined to neurons and dendrites [ 11 ].…”

“…GLP-1RAs are overall well-tolerated, with their most common adverse effects being nausea, vomiting, and diarrhea [ 7 ]. It has been recently shown that there are cholecystokinin-expressing neurons in the caudal brainstem, which are activated postprandially and are responsive to GLP-1RAs, explaining in part the body weight-lowering effects of GLP-1RAs but also their ability to induce nausea [ 12 ].…”

“…GLP-1RAs reduce glycemia in patients with T2DM by increasing glucose-induced insulin secretion and inhibiting glucagon secretion via the stimulation of pancreatic GLP-1 receptors in beta and alpha cells and by increasing insulin sensitivity [5]. GLP-1 and its analogues can also amplify insulin signaling in brain cells, leading to increased insulin sensitivity in neurons [7,8]. Within the cardiovascular system, GLP-1 receptors are expressed on endothelial cells, monocytes, macrophages, and vascular smooth muscle cells (VSMCs) [9].…”

GLP-1 Receptor Agonists in Neurodegeneration: Neurovascular Unit in the Spotlight

“…In addition to the direct effects on the cellular elements of the NVU, ancillary mechanisms of neuroprotection by GLP-1RAs may indirectly emanate from the attenuation of pathological processes in the periphery, in particular, favourable outcomes associated with GLP-1RAs on glucose and lipid metabolism, cardiovascular function and systemic inflammation [3,4,241]. As discussed above, the existing literature in animal models of Aβ amyloidosis and tauopathies indicates that the long-term activation of GLP-1 signalling attenuates protein aggregation in the brain (Table 2).…”

Mitophagy: A potential therapeutic target for insulin resistance

“…In a study of monocytes, metformin activated AMPK-induced mitophagy to restore normal mitochondrial function, thereby improving pancreatic beta cell function and IR ( Bhansali et al, 2020 ). Glucagon-like peptide-1 (GLP-1) receptor agonists can activate the GLP-1 receptor, enhance insulin secretion in a glucose-dependent manner, inhibit glucagon secretion, delay gastric emptying, and reduce food intake through central inhibition of appetite, thereby achieving hypoglycemic effects ( Laurindo et al, 2022 ). Liraglutide, an important GLP-1 receptor agonist, may play a key role in maintaining mitochondrial homeostasis by regulating PINK1/Parkin-mediated mitophagy and inhibiting PINK1/Parkin overexpression ( Zhang et al, 2022 ).…”