Plasma levels of glucagon but not GLP-1 are elevated in response to inflammation in humans

Abstract

Objective: Glucagon and glucagon-like peptide-1 (GLP-1) originate from the common precursor, proglucagon, and their plasma concentrations have been reported to be increased during inflammatory conditions. Increased blood glucose levels are frequently observed in septic patients, and therefore we hypothesized that glucagon, but not GLP-1, is increased in individuals with inflammation. Design: Prospective longitudinal cohort study. Materials and Methods: We measured glucagon and GLP-1 in plasma sampled consecutively in three cohorts consisting of patients with infective endocarditis (n=16), urosepsis (n=28) and post-operative inflammation following percutaneous aortic valve implantation or thoracic endovascular aortic repair (n=5). Correlations between C-Reactive Protein (CRP), a marker of systemic inflammation, and glucagon and GLP-1 concentrations were investigated. Additionally, glucagon and GLP-1 concentrations were measured after a bolus infusion of lipopolysaccharide (LPS, 1ng/kg) in nine healthy young males. Results: Glucagon and CRP were positively and significantly correlated (r=0.27; P=0.0003), whereas no significant association between GLP-1 and CRP was found (r=0.08, P=0.30). LPS infusion resulted in acute systemic inflammation reflected by increased temperature, pulse, tumor necrosis factor-α (TNFα), interleukin-6 (IL-6) and concomitantly increased concentrations of glucagon (P<0.05) but not GLP-1. Conclusions :Systemic inflammation caused by bacterial infections or developed as a non-infected condition is associated with increased plasma concentration of glucagon, but not GLP-1. Hyperglucagonemia may contribute to the impaired glucose control in patients with systemic inflammatory diseases.

Prolonged lipopolysaccharide‐induced illness elevates glucagon‐like peptide‐1 and suppresses peptide YY: A human‐randomized cross‐over trial

“…The systemic effect of the initial dose of LPS (1 ng kg −1 at time point −24 h) has already been reported elsewhere (Modrzynska et al, 2021), and included a marked increase in heart rate (peak increase ≈ 25 beats per min), temperature (peak increase ≈ 2°C), inflammatory cytokines (peak increase in TNF-α ≈ 150 pg ml −1 and IL-6 ≈ 400 pg ml −1 ), and symptom scores (Table 1). We have previously validated this human model of SI and showed it causes insulin resistance (Mose et al, 2020).…”

“…Previous studies have demonstrated elevated GLP-1 levels during inflammation (Brakenridge et al, 2019;Perl et al, 2018), but a recent clinical study from our group found that GLP-1 concentrations decrease during the first 6 h of LPS exposure in healthy young men (Modrzynska et al, 2021). In addition, clinical data from patients with endocarditis, urinary tract infection, noninfectious and postoperative inflammation show divergent correlations between inflammation (using CRP) and GLP-1.…”

Proinflammatory cytokine-induced alpha-cell impairment in human islet microtissues is partially restored by dual incretin receptor agonism

“…Although post-prandial (i.e., high glucose) glucagon hypersecretion has been described early in type 1 diabetes disease progression [44], short-term cytokine exposure did not appear to reflect a type 1 diabetes phenotype with regards to the hypoglycaemic state (low glucose), characterised by reduced glucagon secretion [3–6]. This increase in glucagon secretion may reflect an initial response to cytokines, as increased glucagon has been shown to correlate with inflammation [45]. Alternatively, the increased glucagon secretion may reflect alpha-cell dysfunction preceding beta-cell loss, as described for autoantibody-positive donors [46].…”

Improvement of liver metabolic activity in people with advanced HIV after antiretroviral therapy initiation

“…Factors that negatively correlated with SUV mean included inflammatory markers and glucagon levels. This could hypothetically reflect stimulation of glucagon levels by hypoglycemia and systemic inflammation [45][46][47] in the acutely sick PWH at baseline, with an eventual reduction as inflammation decreases during recovery following ART initiation.…”