Abstract
The incretin hormone glucagon-like peptide 1 (GLP-1) has neuroprotective effects in animal models of Parkinson’s disease (PD), and GLP-1 receptor agonists are associated with clinical improvements in human PD patients. GLP-1 is produced and secreted by intestinal L-cells in response to consumption of a meal. Specifically, intestinal microbiota produce short chain fatty acids (SCFA) which, in turn, promote secretion of GLP-1 into the systemic circulation, from which it can enter the brain. Our group and others have reported that PD patients have an altered intestinal microbial community that produces less SCFA compared to age-matched controls. In this report, we demonstrate that PD patients have diminished GLP-1 secretion in response to a meal compared to their household controls. Peak postprandial GLP-1 levels did not correlate with PD disease severity, motor function, or disease duration. These data provide the scientific rationale for future studies designed to elucidate the role of GLP-1 in the pathogenesis of PD and test the potential utility of GLP-1-directed therapies.
Highlights
Parkinson’s disease (PD) is an unrelenting, progressive neurodegenerative disease that affects 1– 2% of the population over 60 years of age, with incidence rising in recent years (Kalia and Lang, 2015; Marras et al, 2018; Yang et al, 2020)
Our data demonstrate that compared to healthy subjects, PD patients have a diminished capacity to secrete glucagonlike peptide 1 (GLP-1) into the systemic circulation in response to a meal
Data published by our group and others demonstrate that PD patients have an altered intestinal microbiome associated with reduced short chain fatty acids (SCFA) levels, and this alteration could contribute to the observed blunted GLP-1 response (Keshavarzian et al, 2015; Unger et al, 2016; Sun and Shen, 2018)
Summary
Parkinson’s disease (PD) is an unrelenting, progressive neurodegenerative disease that affects 1– 2% of the population over 60 years of age, with incidence rising in recent years (Kalia and Lang, 2015; Marras et al, 2018; Yang et al, 2020). Follow-up studies demonstrate that systemic administration of Exendin-4 preserves motor function, decreases microglial activation, and inhibits inflammatory cytokine expression induced by MPTP in mice (Kim et al, 2009), rescues nigrostriatal dopaminergic neurons from the effects of 6OHDA in rats (Bertilsson et al, 2008), and a sustained release formula (PT320) delays progression of PD-like symptoms in a genetic mouse model of PD (Wang et al, 2021). Colonization of mice with bacteria (Lactococcus lactis, MG1363) that constitutively produce GLP-1 protects mice from MPTPinduced effects (Fang et al, 2020) These data are corroborated in PD patients, who, when treated with the GLP-1 receptor agonist exenatide, demonstrate improvements in motor function that are sustained beyond the treatment period (Athauda et al, 2017, 2018, 2019). These data suggest that GLP-1 may influence PD pathogenesis and progression
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
