Recent advances in understanding the role of glucagon-like peptide 1

Abstract

The discovery that glucagon-like peptide 1 (GLP-1) mediates a significant proportion of the incretin effect during the postprandial period and the subsequent observation that GLP-1 bioactivity is retained in type 2 diabetes (T2D) led to new therapeutic strategies being developed for T2D treatment based on GLP-1 action. Although owing to its short half-life exogenous GLP-1 has no use therapeutically, GLP-1 mimetics, which have a much longer half-life than native GLP-1, have proven to be effective for T2D treatment since they prolong the incretin effect in patients. These GLP-1 mimetics are a desirable therapeutic option for T2D since they do not provoke hypoglycaemia or weight gain and have simple modes of administration and monitoring. Additionally, over more recent years, GLP-1 action has been found to mediate systemic physiological beneficial effects and this has high clinical relevance due to the post-diagnosis complications of T2D. Indeed, recent studies have found that certain GLP-1 analogue therapies improve the cardiovascular outcomes for people with diabetes. Furthermore, GLP-1–based therapies may enable new therapeutic strategies for diseases that can also arise independently of the clinical manifestation of T2D, such as dementia and Parkinson’s disease. GLP-1 functions by binding to its receptor (GLP-1R), which expresses mainly in pancreatic islet beta cells. A better understanding of the mechanisms and signalling pathways by which acute and chronic GLP-1R activation alleviates disease phenotypes and induces desirable physiological responses during healthy conditions will likely lead to the development of new therapeutic GLP-1 mimetic–based therapies, which improve prognosis to a greater extent than current therapies for an array of diseases.

Circulating GLP-1 Levels as a Potential Indicator of Metabolic Syndrome Risk in Adult Women

“…Moreover, the FGF21 molecules secreted by iNKT cells play an important role in activating the thermogenic process in brown adipose tissue [ 37 ]. Inhibitors of DPP-4 (the enzyme that deactivates GLP-1) and GLP-1 analogs that have functions similar to those of GLP-1 have been commercialized for the treatment of diabetes [ 12 , 38 ] and have also recently been used for the treatment of obesity [ 12 , 38 , 39 , 40 ]. In addition to the GLP-1R in the pancreas, GLP-1 can bind to its receptor in various other organs (e.g., brain, stomach, muscles, liver, and heart) to perform diverse functions [ 36 ].…”

Alleviation of Depression by Glucagon-Like Peptide 1 Through the Regulation of Neuroinflammation, Neurotransmitters, Neurogenesis, and Synaptic Function

“…Chronic administration reduced depression-like behavior (Anderberg et al, 2016) 2012; Darsalia et al, 2014a;Augestad et al, 2020;Reed et al, 2020). In addition, GLP-1 can boost immune cell infiltration as well as the production of pro-inflammatory cytokines under inflammatory conditions (Liu et al, 2009;Parthsarathy and Holscher, 2013b).…”

“…GLP-1 has been reported to promote the production of anti-inflammatory cytokines in various organs including the adipose tissue and pancreas, and the brain ( Dobrian et al, 2011 ; Lee et al, 2012 ; Darsalia et al, 2014a ; Augestad et al, 2020 ; Reed et al, 2020 ). In addition, GLP-1 can boost immune cell infiltration as well as the production of pro-inflammatory cytokines under inflammatory conditions ( Liu et al, 2009 ; Parthsarathy and Holscher, 2013b ).…”

A Review of Current Trends with Type 2 Diabetes Epidemiology, Aetiology, Pathogenesis, Treatments and Future Perspectives

“… 255 , 256 GLP-1R agonists used in T2D treatment are either derivatives of native GLP-1 (liraglutide, albiglutide, semaglutide and dulaglutide), which have been modified to be resistant to DPP-IV inactivation or derivatives of exendin-4 (exenatide, lixisenatide and exenatide-LR). 257 , 258 Exendin-4 was originally isolated from the saliva of the Gila monster lizard and is resistant to the action of DPP-IV. 257 , 259 Key pharmacological and clinical features of clinically available GLP-1R agonists are presented in Table 3 and Figure 8 compares the amino acid sequence of native GLP-1 and the GLP-1 analogues liraglutide and exenatide.…”

“… 257 , 258 Exendin-4 was originally isolated from the saliva of the Gila monster lizard and is resistant to the action of DPP-IV. 257 , 259 Key pharmacological and clinical features of clinically available GLP-1R agonists are presented in Table 3 and Figure 8 compares the amino acid sequence of native GLP-1 and the GLP-1 analogues liraglutide and exenatide.…”